Formation and propagation of brain oedema fluid around human brain metastases. A CT study

Summary Computerized tomography (CT) was used to examine the timecourse of the propagation of extravasated contrast medium from small brain metastases into the peritumoural oedematous white matter, following infusion of 200 ml of meglumine amidtrizoate for 3 hours. Four patients with a metastatic brain tumour were examined. CT scans at identical levels were taken 1.5, 3, 6, 9, and 12 hours after start of contrast infusion. Following 4–7 days of dexamethasone treatment (8–12mg/day i.v.) the examination was repeated. A contrast-enhanced area was observed surrounding the clearly delineated tumours, expanding gradually in a circular fashion into the peritumoural white matter oedema. The expanding circular enhancement was measured planimetrically on the various scans. From these values, the increase in radius/hr respectively in volume/hr was calculated, assuming a spherical geometry. This enabled a determination of the rate of oedema fluid formation and of the speed of oedema fluid propagation. The formation rate of oedema fluid amounted to 0.5–3.2ml/hour and the speed of oedema fluid spreading to 1.9 mm/hour. Following treatment with dexamethasone the formation rate of oedema fluid is reduced by 30–50%. The important clinical implications of these new findings are discussed.     

Factors affecting the extension of peritumoural brain oedema. A CT-study

Summary In human brain tumours the extension of peritumoural brain oedema may vary considerably. 37 brain tumours of various pathology and 2 abscesses were examined to identify the factors and mechanisms responsible for the oedema spreading. Peritumoural oedema profiles were determined towards the white matter and ventricle by measuring the CT-numbers of consecutive tissue blocks of 3.0–3.6 mm from the tumour to the normal white matter or the ventricle. It was found that neither the size of the tumour nor the histology has a close relationship to the amount of peritumoural oedema. The distance of oedema spreading rather is determined by the amount of fluid accumulation in the white matter immediately bordering the tumour. This relationship corresponds to a semilogarithmic function and represents the relation between the tumour-adjacent accumulation of extracellular fluid volume and the distance of extracellular fluid movement. The analysis of this relation leads to the suggestion that pressure gradients and bulk flow are involved in the development of human peritumoural oedema.     

Resorption of peritumoural oedema in cerebral gliomas during dexamethasone treatment evaluated by NMR relaxation time imaging

Summary Peritumoural brain oedema is a prominent feature of malignant brain tumours. Glucocorticoids diminish the neurological symptoms and signs caused by the oedema and reduce the abnormally high cerebral water content. The exact mechanisms of action of the glucocorticoids are unknown.The present study investigates the influence of dexamethasone on NMR relaxation time T₁ in peritumoural oedema in 13 patients with gliomas. It is shown that NMR T₁ images can be used as a potent monitor of brain oedema, and that dexamethasone significantly reduces mean T₁ after 1, 3, and 7 days of treatment by 2%, 6%, and 13% respectively.Using an image histogram analysis technique the term superoedema was defined as the 50% of the total oedema area with the highest t₁, corresponding to the highest water content. It is shown, that with this technique the treatment effect of steroids on superoedema was a reduction of 13%, 33%, and 57% after 1, 3, and 7 days of treatment respectively. The mean change after 24 hours of treatment was statistically significant (p < 0.01).The method can be used in all situations where the anti-oedematous effect of a given treatment is to be monitored.     

Cystic meningioma: Neuroradiological (MRI, CT) and macroscopic intraoperative appearance. A case report

Differential diagnosis of intracranial cystic meningiomas may present difficulties in about 10–15% of cases where anatomo-pathological alterations such as intratumoral necrosis, cystic cavity, hemorrhage or lipomatous infiltration are present. These alterations are responsible for an unusual radiological appearance which may suggest a false diagnosis. We describe a case of meningioma with a cystic appearance in which MRI was more helpful than CT, because it suggested an extra-axial meningiomatous lession and thus allowed more precise surgical planning.     

Intracranial hypertension and brain oedema in albino rabbits

Summary Increased intracranial pressure due to brain oedema was produced in albino rabbits by combining a cryogenic lesion in the left hemisphere with the intraperitoneal administration of 6-aminonicotinamide (cytotoxic agent).The most effective reduction in ICP (74%) was achieved when furosemide and mannitol were used in combination. When either mannitol or furosemide was employed alone, the average ICP reduction was approximately 53%. Peak ICP reduction occurred at 45 minutes with furosemide, 30 minutes with mannitol and furosemide combined, and at 60 minutes with a combination of mannitol and acetazolamide.Also studied simultaneously in these animals were intracranial elastance (Em), brain water content, hemispheric water volume content, electrolytes, EEG, and gross pathology. Following therapy there was a statistically significant reduction of water content in the left hemisphere (cryogenic lesion) by all therapeutic modalities except with furosemide alone. In the right hemisphere the water content was reduced by furosemide and the furosemide-mannitol combination but not by the association of mannitol with acetazolamide. A significant decrease of brain sodium was noted only for the combination of mannitol and furosemide.This study indicates that effective reduction of cytotoxic-cryogenic brain oedema and intracranial hypertension can be obtained with a variety of diuretic agents. From the standpoint of tissue dehydration, restoration of tissue electrolyte balance, and rate of ICP reduction, the combination of furosemide-mannitol appears to offer advantages over furosemide alone, or acetazolamide-mannitol.     

Brain oedema in patients with intracranial meningioma

Summary The authors analysed the correlation between different clinical, radiological, and pathological variables and the presence and intensity of brain oedema associated to intracranial meningioma in 400 consecutive patients studied by computerized tomography (CT).The following factors did not show significant correlation with brain oedema development: the age and sex of the patient, the occurrence of focal deficits, the presence of skull changes (endostosis, exostosis, osteolysis), the occurrence of tumour calcification, the density of the tumour on plain CT scan, the presence of a cystic component, the pathological subtype of meningioma (both conventional and non-conventional), and the presence of histological features of tumour aggressiveness, such as an increased vascularization, high cellularity, high mitotic index, pleomorphism, necrosis, and brain infiltration.Factors showing a statistically significant correlation with the presence and intensity of brain oedema at the bivariate analysis were: the presence of symptoms (p < 0.001), the duration of the clinical history (p < 0.05), the location and size of the tumour (p < 0.001), the type (heterogeneous vs homogeneous), and intensity of tumour contrast enhancement (p < 0.001), the presence of irregular tumour margins (p < 0.001), and the existence of focal low density intratumoural areas (p < 0.001).The multivariate analysis using only clinical parameters showed that the group of variables with the highest power for predicting the presence of brain oedema (concordance level of 76.8%) included: the presence of symptoms, the occurrence of seizures (focal or generalized), the presence of an intracranial hypertension syndrome, and the age of the patient. The multivariate analysis using only anatomico-radiological parameters showed that the model which included the size of the tumour, the intensity of contrast enhancement, the tumour margins, and meningioma location, predicted the presence of brain oedema in 80.8% of the cases.Though the results of the present study do not definitively support any of the major physiopathological theories proposed to explain brain oedema formation in patients with intracranial meningioma, some findings could favour the so-called hydrodynamic theory.     

Intracranial meningiomas in the elderly in the CT scan era

Summary Intracranial meningiomas diagnosed and operated upon in similar five-year periods before and after CT scan are analysed. In the latter period the overall number of meningiomas and the average age of the patients have increasedtumours from 77 to 186, and average age from 50 to 56. All patients but one from the first group were operated on, while only 155 from the second group underwent surgery. Operation was rejected in 31 patients for different reasons. In the pre-CT scan epoch 25% of patients who were operated on were over 60 and 9% were over 65, whereas in the CT scan era these rates have risen to 35 and 21% respectively. Mortality and good recovery rate were the same in both groups up to 65 years of age.After 65, postoperative complications and mortality increased steeply: of the patients over 65 in whom the growth was excised 55% died. The radical surgery of intracranial meningiomas in geriatric patients over 65 still remains a tremendous challenge despite all the advances in operative technique, neuroanaesthesia and intensive care. On these grounds, in such patients surgical indications should be carefully evaluated.     

The effect of intraventricular albumin in experimental brain oedema

Summary Therapy for vasogenic brain oedema (VBE) is still an unsolved problem. Experimental work with the aim of establishing an oncotherapeutic option is presented.VBE is performed by focal freeze injury in rats. Using a stereotactic head holder hypo- or hyperosmolar human serum albumin is administered via the intraventricular route. The goal is to enhance the migration of oedema fluid with the aid of oncotic pressures. Early and late results are obtained for each group respectively four and twenty-four hours after the infliction of cold injury. The efficacy of therapy is evaluated by cerebrospinal fluid (CSF) osmolality, cerebral water content, tissue specific gravity, and blood-brain barrier (BBB) permeability. Posttherapeutic values for CSF osmolality are obtained by cisterna magna puncture.Hyperosmolar CSF after performance of cold injury (p < 0.05) is thought to be a result of fluid accumulation in the traumatized region partially from the intraventricular space. Posttherapeutic values after hyperosmolar albumin administration have revealed iso-osmolar CSF, increase in specific gravity (p < 0.001), and decrease in BBB permeability (p < 0.05). These results are in accordance with withdrawal of oedema fluid into the ventricles which can be interpreted as a positive therapeutic effect. Late results in hyperosmolar group have disclosed a hypo-iso-osmolar CSF, persistent increase in specific gravity, and no regression. These values have shown that hyperosmolar albumin administration does not interfere with CSF circulation. Early results of hypo-osmolar albumin application are discouraging.This preliminary work of a therapeutic trial on VBE may be a basis for future investigations with different dosages and time modalities.     

Attenuation of cryogenic induced brain oedema by arginine vasopressin release inhibitor RU51599

Summary Centrally released arginine vasopressin (AVP) has been implicated in the regulation of the brain water content and is elevated in the cerebrospinal fluid of patients with ischaemic and traumatic brain injuries. The protective effect of RU51599, which is a selective kappa opioid agonist as an AVP release inhibitor, on brain oedema was examined. Male Wistar rats, weighing 300 to 400 g each, were used. The cortical cryogenic injury was produced by application of a previously prepared metal probe cooled with dry ice to the dura of the right patietal region. Animals were separated into three groups. Group 1: sham operated rats without lesion production. Group 2: saline-treated rats with lesion production. Group 3: RU51599-treated rats with lesion production. In Group 3, rats were treated with RU51599 (0.1–3 mg/kg) at 30 minutes before lesion production, 1 hour, 2 hours, and 4 hours after lesion production. After 6 hours, animals were decapitated and brain water contents were measured using the dry-wet weight method. The extent of blood brain barrier (BBB) disruption was determined by assessment of Evans blue uptake based on extraction from tissue using dimethylformamide. The primary injured infarcted area was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Sodium and potassium contents in serum and brain tissue were measured using atomic absorption spectrophotometry. The antagonism of naloxone against protective effects of RU51599 on cryogenic induced brain oedema and on antinociceptive effects in acetic-acid treated animals was examined. Statistical analysis was performed using Dunnett-test and U-test following Kruskal-Wallis test. RU 51599 significantly reduced the brain water contents on the injured side and the contralateral non-injured side (p<0.01) after 4 administration of 1 and 3 mg/kg. RU51599 neither significantly inhibited BBB disruption nor reduced the primary injured infarcted area. RU51559 significantly increased brain sodium and potassium contents in the injured brain and also increased serum sodium levels (p<0.01). Naloxone antagonized the anti-oedema effects and antinociceptive effects of RU51599. These findings indicate that the AVP release inhibitor, RU51599 posssibly mediated by opioid receptors, has a potential protective effect on cryogenic-induced brain oedema and that centrally released AVP plays an important role in the progression of vasogenic brain oedema.     

Peritumoural brain oedema in intracranial meningiomas: Influence of tumour size, location and histology

Summary Peritumoural brain oedema was examined retrospectively in 175 patients with 179 intracranial meningiomas. The influence of tumour size, location and histology were investigated.Tumour volume and localization, and the presence of peritumoural brain oedema (PTBOe) were determined by computed tomography (CT). The oedema-tumour volume ratio was defined as Oedema Index (Oel). All patients underwent microsurgical removal of the tumour. Surgically resected meningiomas were classified histopathologically based on criteria of the new World Health Organization (WHO) classification. A close relationship was found between the tumour size and the incidence of peritumoural oedema: with increasing size of the tumour the incidence of oedema also rises, the oedema index, however decreases. Frontobasal and temporobasal meningiomas showed a significant increase in the oedema incidence and the mean oedema index. If major parts of the surface of meningiomas were adjacent to subarachnoid cisterns only a slight tendency for the development of oedema was observed. WHO-III-meningiomas showed a significantly higher oedema incidence (61.1% vs. 94.4%; p<0.004) and mean oedema index (Oel=2.7 vs. 3.7; p<0.0009) than WHO-I-meningiomas. Brain tissue was affected in 59 cases. 19 meningiomas with infiltration into adjacent brain parenchyma revealed a statistically significant increase in oedema incidence (94.7% vs. 51.7%; p<0.0003) and mean oedema index (Oel=3.9 vs. Oel=2.2; p<0.0001) when compared to tumours without any brain tissue involvement in the histopathological specimens. Tumours with large volume, fronto-temporo-basal location and anaplastic histology were not only associated with the highest incidence of oedema formation but also presented with an overproportionate infiltrative growth. Thus, a disruption of the arachnoid or a true brain infiltration may be an essential factor for the development of a PTBOe.     

Peritumoral oedema and lipid content

Summary The authors analyzed the water and lipid contents of oedematous tissues of white matter obtained during the operation, comparing with the absorption value in the CT scan. As the absorption value lowered its level, the water content increased, while the lipid decreased. However, after subtracting these two components, the content of protein also showed a significant decrement parallel to the absorption value despite the existence of extravasated protein. The decrement of lipid content was considered to be due to a dilution effect by an expanded volume of extravasated oedema fluid, as well as the decrease in protein, rather than the actual loss of tissue component; that is demyelination. It is the relative decrease in protein content which contributes to the low absorption value of oedematous tissue.     

Cerebral physiological and biochemical changes during vasogenic brain oedema induced by intrathecal injection of bacterial lipopolysaccharides in piglets

Summary. Summary.   Background: The objective of the study was to evaluate biochemical and physiological changes in an experimental model of vasogenic brain oedema utilising techniques also used in routine neuro-intensive care.   Method: 32 piglets were randomised to control or experimental group. The latter received an intrathecal injection of lipopolysaccharide (LPS) from E.coli (LPS group). Intracranial pressure (ICP) and mean arterial pressure (MAP) were measured continuously. Intracerebral microdialysis was used for analysing interstitial levels of glucose, pyruvate, lactate, glutamate, glycerol and urea every 30 min. Repeated calculations of mean hemispheric CBF were performed utilising an extra-cranial scintillation detector and intracarotid injection of ¹³³Xe. Cerebral specific gravity was measured and the brains were fixed for histological examinations.   Findings: After LPS injection ICP increased reaching a plateau phase after 4–7 hours and CBF increased by 46%. Histological examination showed inflammation with pronounced extravasation of granulocytes. A significant decrease in brain specific gravity (p= 0.022) was obtained. LPS caused a significant decrease in cerebral interstitial concentration of glucose (p=0.0035), and significant increases in lactate concentration (p=0.002) and lactate/pyruvate ratio (p=0.0017). A small but significant increase in glutamate was obtained (p=0.0219). Glycerol did not change significantly.   Interpretation: Intrathecal LPS caused an inflammatory reaction with extravasation of granulocytes, increased blood-brain barrier permeability and cerebral oedema. Biochemical analyses indicate increased glycolysis but no signs of cell membrane degradation. Published online June 20, 2002     

Acute effects of a pedicled omental graft on cold-induced brain oedema in cats

Summary When used as a phrophylactic measure and in chronic experiments, omental transposition has been shown to reduce ischaemic and traumatic oedema in the spinal cord and ischaemic oedema in the brain. We designed this experiment to evaluate the acute effects of a pedicled omental graft on cold-induced brain oedema in cats. Focal oedema was induced in the left frontoparietal region of the brain of nine anaesthetized cats. In five cats, a laparotomy was done and a pedicled omental graft was placed on the lesioned left hemisphere immediately after the cold lesion was made. All cats were sacrificed 72 hours later, and the water content of the white matter was determined in the lesioned and the normal hemispheres. The mean water content of the lesioned hemisphere of the treated group of animals was not significantly different from that of the control group. We conclude that a pedicled omental graft failed to reduce vasogenic oedema in an acute model and probably has no role in the acute management of brain oedema.     

Stereoscopic study on capillary density of early brain oedema in a dog postburn model

Background

After severe burn, the effective circulating blood volume decreases drastically due to massive body fluid loss, and blood redistribution occurs to maintain sufficient blood supply to vital organs. Blood perfusion of brain tissue changes and the permeability of the blood brain barrier increases due to ischaemia and hypoxia, which results in brain oedema. The goal of this study was to explore the changes of cerebral blood flow during the brain oedema at the early stage of severe burn.

Methods

Twenty-six dogs were randomly divided into control and 6, 12, 18, and 24 PBH groups. The manifestation of MRI and histopathology, changes of brain water content were investigated; the shapes and distribution of the cerebral capillaries were observed with the endogenous AKP histochemical staining method and image analysis technique. The volume, surface, and length fractions of cerebral capillaries were tested and analysed with a stereographic method in each group, respectively.

Results

The earliest changes of cerebral oedema were found at 12 PBH with MRI, which showed the brain swelling as characteristic of cerebral morphological changes. The decrease of SIR on T₁WI was not observed until it was above 10%. Signal of T₂WI increased for 8.29% at 24 PBH. Histological changes were observed as early as 6 h after burn, accompanied by swelling of endothelial cells and peri-vascular astrocytes, vacuolation took place in neurons at 12 h after burn, necrosis of different degrees in capillary endothelium, neurons, and axons. Increase in cerebral water content was noted at 6 h postburn, and it was the most marked in 24 postburn group.The distributional density of capillaries became thicker at 6 h and 12 h postburn, the shapes were normal. The capillaries became sparser at 18 h, and almost disappeared from view, only a few ends of capillaries in the shape of vine were seen at 24 h postburn. The percentages of capillary volume, surface, and length fractions were increased at 6 h and 12 h, but decreased at 18 h and reached the lowest point at 24 h postburn (P < 0.05).

Conclusion

We suggest that the changes of cerebral blood flow might play an important role in the pathogenesis of brain oedema in the early stage of severe burn.     

CT表现为非典型性非恶性脑膜瘤的病理学探讨

我们对45例CT表现为非典型病理诊断为非恶性的脑膜瘤，采用细胞核仁组成区嗜银蛋白技术进行观察。结果表明．其中48．9%的Ⅱ级脑膜瘤（WHO）分级）虽非恶性，但细胞核仁组成区嗜银蛋白的数量、大小分布及异常形态变化与Ⅰ级者有明显差异，两者呈直线相关关系。提示CT表现为非典型性Ⅱ级脑膜瘤有明显的潜在增殖能力。推断可藉此预测CT表现为非典型性非恶性脑膜瘤的复发机率。     

Brain oedema induced by ventricular puncture

Summary After ventricular catheterization magnetic resonance (MR) imaging very often demonstrates a focal area of high signal along the drain track which corresponds to parenchymal oedema. This high signal seemed to be more pronounced when the frontal area was catheterized than when the junctional parieto-temporo-occipital parenchyma (or trigonal area) was catheterized. In order to confirm this impression, we prospectively studied 41 consecutive patients with normal-pressure hydrocephalus in whom both of these brain regions were catheterized for intracranial pressure monitoring. Each patient was evaluated by serial MR. The extent of the MR hypersignal induced by both catheterizations was computed from digitized MR masks. The extent of the MR high signal area was significantly greater when the frontal area was catheterized compared to the trigonal area suggesting that the frontal area could be more prone to injury.     

CT与MRI对直肠间质瘤的诊断价值

目的评价CT和MRI对直肠同质瘤的诊断价值及临床意义。方法回顾性分析2000—2006年间收治12例经病理证实的直肠同质瘤的CT及MRI表现，并与手术及病理所见对照。结果肿瘤平均直径7．5cm（3～18cm）；均发生于直肠中下段（12／12）。黏膜下型占16．67％（2／12）；肌壁间型41．67％（5／12）；浆膜下型41．67％（5／12）。病理分型：高危50．0％（6／12），中危33．3％（4／12），低危16．7％（2／12），极低危为0。典型CT与MRI表现为圆形或分叶状肿块，边界清晰，外生性倾向，对周围脏器以推移改变为主；血供丰富，密度不均，有环靶囊变；无淋巴结转移。结论直肠间质瘤的CT与MRI表现具有一定特征。MRI对病灶内部成分的检出及显示肿块浸润范围优于CT。术前CT与MRI检查对治疗方案的选择具有重要意义。     

Adverse biochemical and physiological effects of prostacyclin in experimental brain oedema

BACKGROUND: Prostacyclin (PGI2) and its stable analogues are known to reduce capillary hydraulic permeability. This study explores the biochemical and physiological effects of i.v. infusion of low-dose PGI2 in an experimental model of vasogenic brain oedema. METHODS: Twenty-seven anaesthetized and mechanically ventilated piglets with brain oedema induced by intrathecal injection of lipopolysaccharide (LPS) were used. Five of the animals received a continuous infusion of PGI2 (1 ng kg(-1) min(-1)) i.v. Four microdialysis catheters were placed in the brain to measure interstitial concentrations of glucose, lactate, and glycerol. Mean arterial pressure (MAP), intracranial pressure (ICP) and temperature were monitored continuously. Low-dose infusion of PGI2 started 1 h before the LPS injection and was constant during the study period. RESULTS: Intracranial pressure increased significantly in animals treated with PGI2. The increase in ICP was associated with significant cerebral biochemical changes: decrease in glucose, increase in lactate, increase in lactate/glucose ratio and increase in glycerol. CONCLUSION: In LPS-induced brain oedema i.v. infusion of low-dose PGI2 caused a further increase in ICP and a perturbation of energy metabolism, indicating cerebral ischemia and degradation of cellular membranes.     

Intracranial hypertension and brain oedema in albino rabbits. Part 3: Effect of acute simultaneous diuretic and barbiturate therapy

Summary Increased intracranial pressure due to brain oedema was produced in albino rabbits by combining a cryogenic lesion in the left hemisphere with the intraperitoneal administration of 6-aminonicotinamide (cytotoxic agent). The following parameters were assessed: intracranial pressure (ICP), systolic arterial pressure (SAP), central venous pressure (CVP), EEG, brain water and electrolyte content, gross pathology, and blood brain barrier integrity. Acute therapy to reduce ICP was performed by administering a bolus of mannitol (1 gm/kg) and 30 minutes later, also in bolus, frusemide (5 mg/kg). Immediately following the administration of mannitol an infusion of pentobarbitone was commenced; this was continued for one hour so that a total of 10 mg/kg was administered.There was a 50% reduction of ICP at one hour from initiation of treatment. The brains of the animals were extracted immediately upon cessation of therapy (pentobarbitone) and they revealed a significant reduction of water content for the right, uninjured, hemisphere only, when compared to controls; a slight but not significant reduction of the brain sodium and potassium was noted in both hemispheres. There was no change noted in the gross pathology and extent of blood brain barrier breakdown. In all animals epinephrine infusion had to be administered for between 20 and 30 minutes to maintain a SAP over 80 torr. There seems to be no advantage in the simultaneous administration of barbiturates and diuretics for the control of ICP due to brain oedema.     

Correlation and comparison of syndesmosis dimension on CT and MRI

IntroductionVarious methods using CT scan have been described to diagnose distal tibiofibular syndesmotic injuries. However, CT scan does not take into account the amount of cartilage within the distal tibiofibular joint and could therefore lead to false positive results. We present the first study correlating the findings of the distal tibiofibular syndesmosis on CT and MRI scans.MethodsCT and MRI scan of consecutive patients over a period of 18 months, and of a time lapsed less than 12 months between the two imaging modalities, were reviewed. Measurements of the distal tibiofibular syndesmosis were taken according to a previously published study at the level of the distal tibial physeal scar.ResultsTwenty-six ankles from 25 patients were included in this study for analysis. Significant difference between CT and MRI assessments in the overall distal tibiofibular dimensions and in the posterior distal tibiofibular distance for those ankles with evidence of osteoarthritis was found. Interclass correlation coefficients suggest that such methodology was reproducible and reliable.ConclusionWhen the widening found on a CT scan is minor or the diagnosis is equivocal, a contralateral comparative CT or an ipsilateral MRI scan is recommended to prevent misdiagnosis.Level of evidenceLevel IV.