cerebral edema types management and description

cerebral edema

1. CEREBRAL EDEMA

2. Cerebral edema is the pathologic excess of intracellular and/or extracellular fluid in the brain that can be associated with neurological morbidity and mortality. Cerebral edema is the end result of many neurological diseases. Excess fluid can accumulate in the intracellular or extracellular spaces. 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.

3. T he B lood - B rain B arrier The  blood–brain barrier  ( BBB ) is a highly selective  semipermeable  border of  endothelial cells  that regulates the transfer of solutes and chemicals between the  circulatory system  and the  central nervous system , thus protecting the  brain  from harmful or unwanted substances in the  blood . The blood–brain barrier is formed by endothelial cells of the  capillary wall ,  astrocyte  end-feet ensheathing the capillary, and  pericytes  embedded in the capillary  basement membrane . This system allows the passage of some small molecules by  passive diffusion , as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose and  amino acids  that are crucial to neural function.

4. C erebral edema

5. C ytotoxic edema Cerebral infarction or ischemia Meningitis Reye’s syndrome Trauma Seizure Water intoxication Severe hypothermia Various toxins like dinitrophenol , triethylin , isoniazid Causes:

6. MECHANISM During an ischemic stroke, a lack of oxygen and glucose leads to a breakdown of the sodium-calcium pumps on brain cell membranes , which in turn results in a massive build up of sodium and calcium intracellularly . This causes a rapid uptake of water and subsequent swelling of the cells . It is this swelling of the individual cells of the brain that is seen as the main distinguishing characteristic of cytotoxic edema , as opposed to vasogenic wherein the influx of fluid is typically seen in the interstitial space rather than within the cells themselves

7. Nitric oxide (NO) from nitric oxide synthase (NOS) Neuronal NOS produces toxic free radical (early after cytotoxic injury) Endothelial NOS cause vasodilatation and increase blood flow Inducible NOS produce NO and free radical at 24-48 hr after injury NCCa - ATP channel (nonselective cation channel) opened after depletion of ATP, cause cytotoxic edema after ischemia Regulated by sulfonylurea receptor 1 (can be blocked by low dose glibencamide )

8. Loss of normal cellular homeostasis due to ischemia results in failure of Na+/K+ adenosine triphosphatase (inset) and results in the accumulation of intracellular sodium. Free water flows into the cell along the osmotic gradient that is induced by the accumulation of sodium causing intracellular swelling. Illustration of the blood-brain barrier in the setting of cytotoxic edema.

9. Axial CT and MR images in cytotoxic cerebral edema due to right middle cerebral artery ischemic stroke. (A) Non–contrast-enhanced CT scan obtained 8 hours after the ischemic event demonstrates hypodense changes of the right frontal white matter (yellow arrow). (B) Non–contrast-enhanced head CT scan approximately 36 hours post-stroke demonstrates diffuse swelling of the right frontal lobe with increasing hypodensity in region. (C) Fluid-attenuated inversion recovery MR image demonstrates region of edema ( hyperintensity ). (D) T2-weighted MR image shows increased fluid ( hyperintensity )content in the region of edema. (E) Apparent diffusioncoefficient MR image reveals region of cerebral ischemia/ cytotoxic edema ( hypointensity ). (F) Diffusion-weighted MRimage demonstrates restriction( hyperintensity ) in cytotoxic edema that anatomically correlates with the hypointensity seen in apparent diffusion coefficient imaging.

10. VASOGENIC EDEMA CAUSES Primary or secondary brain tumor Brain abscess and encephalitis Trauma Lead poisoning Late stage of cerebral infarction

11. MECHANISMS Vasogenic edema occurs due to a breakdown of the tight endothelial junctions which make up the blood–brain barrier (BBB) . Blood- tumor barrier has abnormal micro vessels that lacks of tight junctions cause plasma leakage into brain’s extracellular space Macromolecular protein produced by tumor has been identified as vascular permeability factor (VPF) and vascular endothelial growth factor (VEGF) High VPF and VEGF gene expression found in glioblastomas, meningiomas and metastases Glucocorticoids can block permeability- enhancing effects of VPF and VEGF and inhibit tumor cell production of VPF and VEGF

12. Breakdown of the tight junctions and opening of the normal blood-brain barrier via abnormal vascular endothelial growth factor expression and other mechanisms allows for pericellular flow and accumulation of plasma ultrafiltrate into the brain interstitial spaces. Illustration of blood-brain barrier derangements found in vasogenic edema.

13. Axial CT and MR images of right frontal metastasis-associated vasogenic edema. (A) Non–contrast-enhanced CT scan demonstrates right frontal white matter hypodensity consistent with peritumoral edema. (B) Non–contrast-enhanced T1-weighted MR image demonstrates hypointensity of the right frontal edema. (C) Postcontrast T1-weighted MR image reveals a right frontal metastatic deposit (enhancing). (D) T2-weighted MR image demonstrates increased fluid content in the region of edema. (E) Fluid-attenuated inversion recovery MR image demonstrates cerebral edema ( hyperintensity ). (F) Apparent diffusion coefficient imaging demonstrates vasogenic edema ( hyperintensity ). (G)Diffusion-weighted image demonstrates no restriction ( hypointensity ), consistent with vasogenic edema.

14. I nterstitial edema CAUSES OF INTERSTIAL EDEMA Hydrocephalus MECHANISM Transependymal flow of water and solute into periventricular extracellular space Interstitial edema occurs in obstructive hydrocephalus due to a rupture of the CSF-brain barrier . This results in trans-ependymal flow of CSF, causing CSF to penetrate the brain and spread to the extracellular spaces and the white matter. Interstitial cerebral edema differs from vasogenic edema as CSF contains almost no protein.

15. The ventricular ependymal (inset) in interstitial edema as seen on coronal brain imaging ( transependymal flow). Hydrostatic pressure from the ventricular space pushes cerebrospinal fluid into the surrounding brain tissue via bulk flow Illustration of interstitial edema.

16. Axial CT and MR images of interstitial ( transependymal ) cerebral edema from obstructive hydrocephalus. (A) Non–contrast-enhanced CT scan demonstrates hypodensity (yellow arrows) radiating from the lateral ventricles (“capping”) associated with hydrocephalus. (B) Fluid-attenuated inversion recovery MR image demonstrates the transependymal flow (yellow arrows) across the lateral ventricles and hydrocephalus.

17. osmotic edema CAUSES OF OSMOTIC EDEMA HEMODIALYSIS SIADH Hypertensive crisis Water intoxication

18. MECHANISM Hyperosmolarity in brain relatively to circulatory then water move into brain along osmotic gradient Normally, the osmolality of cerebral-spinal fluid (CSF) and extracellular fluid (ECF) in the brain is slightly lower than that of plasma. Plasma dilution decreases serum osmolality, resulting in a higher osmolality in the brain compared to the serum. This creates an abnormal pressure gradient and movement of water into the brain, causing edema BBB IS relatively intact Then edema is interstitial in location

19. Osmotic pressure results from a mismatch between osmolarity in the brain (relative hyperosmolarity ) interstitial and cellular compartments relative to plasma (hypo- osmolar ), such as overly rapid correction of hypernatremia. Under these conditions, free water flows along an osmotic gradient from the plasma into the brain. Illustration of the osmotic cerebral edema.

20. 30 ̊elevation of the head in patients is essential for avoiding jugular compression and impedance of venous outflow from the cranium for decreasing CSF hydrostatic pressure. . Head position elevation may be detrimental in ischemic stroke , because it may compromise perfusion to ischemic tissue at risk. to avoid the use of restricting devices and garments around the neck (such as devices used to secure endotracheal tubes), which may impair cerebral venous outflow via compression of the internal jugular veins.

21. Hypoxia and hypercapnia are potent cerebral vasodilator Patient should be intubated in: GCS scores less than or equal to 8 Patients with poor upper airway reflexes be intubated for airway protection. Aspiration pneumonitis Pulmonary contusion Acute respiratory distress syndrome.

22. Maintenance of CPP using adequate fluid management in combination with vasopressors is vital in patients with brain injury Hypotonic fluids should be avoided at all cost Euvolemia or mild hypervolemia with the use of isotonic fluids (0.9% saline) should always be maintained through rigorous attention to daily fluid balance, body weight, and serum electrolyte monitoring.

23. Potent vasodilators are to be avoided Nitroglycerine Nitroprusside as they may exacerbate cerebral edema via accentuated cerebral hyperemia and CBV due to their direct vasodilating effects on cerebral vasculature.

24. controlled hyperventilation is used as therapeutic intervention for cerebral edema , particularly when the edema is associated with elevations in ICP. A decrease in PaCO2 by 10 mmHg produces proportional decreases in CBF resulting in rapid and prompt ICP reduction. The vasoconstrictive effect of respiratory alkalosis on cerebral arterioles has been shown to last for 10 to 20 hours Beyond which vascular dilation may result in exacerbation of cerebral edema and rebound elevations in ICP.

25. The most rapid and effective means of decreasing tissue water and brain bulk. Decrease ICP and increase cerebral blood flow. Mannitol is the most popular osmotic agent. IV Mannitol is given in the dosage of 0.25-1.0 g/kg. Glycerol is another useful agent given in oral doses of 30 ml every 4-6 hour or daily IV 50 g in 500 ml of 2.5% saline solution. Used in a dose of 0.5-1.0 g/kg body weight.

26. Mannitol is a nonelectrolyte of low molecular weight that is pharmacologically inert. can be given in large quantities sufficient to raise osmolarity of plasma. It is not metabolized in the body; freely filtered at the glomerulus and undergoes limited reabsorption: therefore excellently suited to be used as osmotic diuretic. Mannitol appears to limit tubular water and electrolyte reabsorption in a variety of ways

27. The extra- osmotic properties of mannitol provide additional beneficial effects in brain injury, Decreases in blood viscosity, Resulting in increases in CBF and CPP and a resultant cerebral vasoconstriction leading to decreased CBV free radical scavenging Inhibition of apoptosis DOSE OF MANNITOL: The conventional osmotic agent mannitol, when administered at a dose of 0.25 to 1.5 g/kg by intravenous bolus injection, usually lowers ICP, with maximal effects observed 20 to 40 minutes following its administration. Repeated dosing of Mannitol may be instituted every 6 hours and should be guided by serum osmolality

28. CONTRAINDICATIONs for mannitol Acute tubular necrosis, Anuria Pulmonary edema ; Acute left ventricular failure CHF Cerebral haemorrhage. OTHER OSMOTIC DIURETICS Isosorbide and glycerol These are orally active osmotic diuretics which may be used to reduce intraocular or intracranial tension. Intravenous glycerol can cause haemolysis. Dose: 0.5–1.5 g/kg as oral solution.

29. Fundamental goal of osmotherapy is to create an osmotic gradient to cause egress of water from the brain extracellular (and possibly intracellular) compartment into the vasculature thereby decreasing intracranial volume (normal brain volume 80%, normal blood volume 10%, and normal CSF volume 10%) and improving intracranial elastance and compliance. The goal of using osmotherapy is to maintain a euvolemic or a slightly hypervolemic state .

30. The osmotic effect can be prolonged by the use of loop diuretics (Furosemide) after the osmotic agent infusion. Loop diuretics (Furosemide) can be used as an adjunct. Furosemide (0.7 mg/kg) has been shown to prolong the reversal of blood brain osmotic gradient established with the osmotic agents by preferentially excreting water over solute.

31. Lower intracranial pressure primarily in vasogenic edema or accompanying brain irradiation and surgical manipulation because of their beneficial effect on the blood vessel, steroids decrease tight-junction permeability and, in turn, stabilize the disrupted BBB Less effective in cytotoxic edema, and are not recommended in treatment of edema secondary to stroke or haemorrhage . Inj. Dexamethasone 4-6 mg IM every 4-6 hours. Management of malignant brain tumours , either primary or secondary, as adjuvant chemotherapy of some CNS tumours and perioperatively in brain surgery

32. Pain and agitation can worsen cerebral edema and raise ICP significantly, and should always be controlled. Judicious intravenous doses of bolus morphine (2–5 mg) fentanyl (25– 100 mcg) continuous intravenous infusion of fentanyl (25–200 mcg/hour) can be used for analgesia. A NEUROMUSCULAR BLOCKADE: can be used as an adjunct to other measures when controlling refractory ICP. Nondepolarizing agents should be used, because a depolarizing agent (such as succinylcholine) can cause elevations in ICP due to induction of muscle contraction.

33. Hyperthermia is deleterious to brain injury, achieving normothermia is a desirable goal in clinical practice. Air-circulating cooling blankets Iced gastric lavage Surface ice packs

34. Surgical treatment is occasionally recommended for large hemispherical infarcts with edema and life threatening brain-shifts. Temporary ventriculostomy or craniectomy may prevent deterioration and may be lifesaving. Decompressive craniectomy in the setting of acute brain swelling from cerebral infarction is a life saving procedure and should be considered in younger patients who have a rapidly deteriorating neurological status. Severe Hydrocephaus - Ventriculo Peritoneal shunt .

35. Other Adjunct Therapies Barbiturates, Procaine derivatives, Indomethacin, Propofol and THAM (Tromethamine), are some other agents which have been tried and used in the past ,not being used routinely in present practice,