The normal function of the central nervous system (CNS) is protected mechanically by the skull, physiologically by the blood-brain barrier, and chemically by the autoregulation of the blood flow. These mechanisms protect the function of the neurons and glia which are very sensitive to compression, deprivation of blood supply, and exposure to toxic substances. The skull serves to protect the brain. This thick layer of bone is perforated by several foramina and is divided into two large compartments communicating through the tentorial incisura. Because the bone of the calvarium essentially is nondistensible, the volume of the intracranial space is constant, irrespective of the pressure generated within it. The intracranial space is filled to capacity with fluid in and around the brain and blood vessels and solid materials so that its contents are nearly incompressible. These facts represent the basis of the Monro-Kellie doctrine. In general, it means that adding further volume into the skull such as in blood clot or brain swelling will result in a rise in pressure within the skull which will damage normal brain and if it reaches critical levels will result in death. However, there are certain compensatory mechanisms that allow for some increase in volume without change in pressure. This is the basis of the pressure volume curve that varies in individual patients; it can be predicted with only limited accuracy but it explains differences in clinical courses in individual patients with blood clot, brain swelling or tumor.
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Blood is delivered to the brain through a system of conducting and penetrating vessels. The concept of a blood-brain barrier and cerebrospinal fluid barrier has been derived from observations that various compounds that rapidly enter and distribute within most organs and tissues are excluded from the brain and cerebrospinal fluid. This is possible because cerebral capillaries differ anatomically from those of the rest of the body in that they have tight junctions between the endothelial cells and are surrounded by astroglial foot processes. The tight junctions can be said to comprise the anatomical and, probably, the functional blood-brain barrier because the junctions make it extremely difficulty for nonlipid-soluble and some other substances to enter the brain. The cerebral vessels are sensitive to metabolic changes, but are less influenced by the autonomic nervous system than similar blood vessels in other organs. Under normal conditions, blood flows through the brain at a rate of approximately 750 ml/min or 50 ml/100 gm of brain. The cerebral blood flow (CBF) is nearly constant despite wide variations in cerebral perfusion pressure, which is determined by the difference between the arterial and intracranial pressures. The normal range of autoregulation appears to be between 45 and 150 mm/Hg cerebral perfusion pressure. Within the range, CBF is unaffected by systemic pressure because of independent adjustments in the diameters and resistances of the cerebral arterioles. Pressures above the normal limit produces capillary hypertension and dilatation, whereas pressures lower than 40 mm/Hg induce cerebral ischemia. CBF is autoregulated in response to increased intracranial pressure (ICP) in much the same way it is during periods of decreased systemic arterial pressure. Therefore, when autoregulation is intact and ICP is elevated, CBF does not fall until the cerebral perfusion pressure is reduced to less than 40 mm/Hg. Autoregulation is lost when the pH around the cerebral arterioles falls because of cerebral acidosis such as may occur in head trauma. Marked acidosis maximally dilates the arterioles and abolishes or reduces their responsiveness to systemic blood pressure. In fact, when autoregulation is defective, CBF varies linearly with perfusion pressure. Alteration of the pCO2 will have a major effect on CBF. For example, increasing pCO2 from 20 to 40 will double the cerebral blood flow by dilating the arterioles and increasing both blood volume and blood flow. In head-injured patients, however, the increased pCO2of the blood actually may reduce the cerebral circulation in the damaged areas. This may occur when the vessels in the injured areas are dilated maximally owing to tissue acidosis and only the vessels in healthy areas can dilate in response to raised arterial pCO2. The result is blood shunted through or from the impaired areas, a phenomenon called the luxury perfusion syndrome or intracerebral steal syndrome.
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The pathophysiological mechanisms operative in patients suffering from brain trauma, either caused by an injury, brain tumor or hemorrhage, are numerous; in many instances, their interrelationships are understood poorly. In all types of injuries, however,
there is trauma to the cells and microvasculature. The degree of injury is determined by the compound effects of the mechanical damage to the cells, disruption of the blood-brain barrier, extravasation of blood, and loss of autoregulation. In addition, blood extravasated within the skull, either within the brain or outside of it, can assume the role of a mass and can cause secondary, often fatal, injury to essential neural structures. Therefore, there are conceptually two categories of injuries.
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In patients with intracerebral, subdural, epidural hematomas, or tumors the deleterious effect on the brain itself is caused primarily by the resulting changes in the pressure volume curve previously discussed as well as by the anatomical structures it involves. Once the intracranial pressure reaches a critical point a vector of forces develops that causes movement of the brain within the skull and through its compartments and which eventually pushes the brain into the naturally present openings between them. The mass of compressed brain then "herniates" and secondarily compresses other initially non-injured vital parts of the central nervous system. The two most common types of herniation are transtentorial and tonsillar. In the first type, the brain stem is compressed by the uncus of the temporal lobe and is pressed against the edge of the tentorium. In the second type, the medulla is compressed by the cerebellar tonsils. In both cases, the cellular structures of the brain stem and medulla are compromised and its vasculature is damaged. This creates new lesions that become independent of the original ones and once developed will lead to death regardless of the treatment.
If the hematoma or a tumor is evacuated surgically before such events take place, secondary injury within the brain stem and the medulla will be prevented and the patient's life would be saved with the extent of neurological injury determined by the extent of damage to local structures caused by the injury or involved by the tumor. Thus a tumor or hemorrhage located in the speech area of the brain will result in the inability to speak while those in motor areas will result in loss of movement of the opposite side of the body. It should be stressed however that strong reparative processes within the brain start "re-educating" the brain soon after an injury and thus in patients who survive there is almost invariably significant neurological improvement. This process that can continue up to 14 to 16 months after an insult almost invariable results in significant improvement in the function and in some patient's even in complete recovery.
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In a closed head injury such as caused by falls or car accidents, there is usually extensive damage caused by shearing of neurons and small petechial hemorrhages. Usually there is no significant mass that can be evacuated surgically and the injury usually is diffuse. Depending on the severity of the injury, the morphological substrates range from transient membrane depolarization to total anatomical disruption of the neurons, glia, and microvasculature. There may be extravasation of a small amount of blood into the brain parenchyma and subarachnoid space. Both of these processes are accompanied by potassium ion (K+) release from the injured cells into the extracellular space and concomitant calcium ion (Ca+) depletion accompanied by release of neurotransmitters. The K+ release, which appears to be transient in most instances, blocks neuronal transmission, causes significant increase in vascular resistance, and induces the uptake of water into the glial and probably into neuronal cells. The decrease in Ca+ affects cell permeability, decreases metabolic activity, and blocks synaptic transmissions. This leads to cellular dysfunction and swelling even outside the damaged area. In addition, the disruption of the blood-brain barrier leads to extravasation of proteinaceous substances and extracellular edema.
Changes in the cerebral vessels always are present to some degree in severe trauma. They include a microvascular constriction, compression, and spasm in major vessels. it appears that the earliest phase in head trauma is accompanied by actual increase in the intracerebral intravascular volume which is thought to be due to the paralysis of the venous system and passive congestion; the last phase is associated with the development of ischemic infarcts. It is not clear whether the ischemic infarcts are caused by a decreased flow through the constricted "spastic" vessels or whether they are the result of massively increased peripheral vascular resistance induced by the changes in the ionic milieu or mechanical compression.
The clinical picture is determined by the local extent and severity of the lesion as well as by its location within the neural axis. Thus, two lesions, comparable to each other in extent and severity, may produce a totally different picture if, for example, one is located in the frontal lobe and the other located within the brain stem. The first may not cause any appreciable neurological deficit while the other may result in deep coma.
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Most types of closed head trauma are accompanied by elevation of intracranial pressure (ICP). There are several stages of the ICP elevation that have different pathophysiological causes and significance. The first increase in ICP takes place during the stage of K+ release and the vasoparalysis. The second is caused by the development of cellular swelling induced by the initial trauma and the profound biochemical changes affecting the cellular membranes and ionic equilibrium. Extravasation of proteins and particles of blood across the damaged blood-brain barrier (BBB) adds to the problem. This is the stage where various treatment modalities including hyperventilation and administration of mannitol and steroids are most effective.
The tertiary and terminal increase in intracranial pressure is caused by the combination of micro- and macroinfarcts, disruption of all cellular function, and the blood-brain barrier. This increase may take place within minutes after injury and be present when the patient arrives in the emergency room. Since there is no effective treatment for the damage caused by deprivation of the neural cell of its metabolic substrates there is no effective way of controlling the tertiary increase in ICP. This increase, however, is not the cause but is the reflection of the cellular dysfunction. Therefore, attempts should be
made to prevent this event from developing rather than trying to treat it. Unfortunately at this point in time, there is no effective treatment of severe head injury.
The role of ICP in head trauma has been reconsidered and new questions constantly are raised. Although the classical concept is that elevated ICP is the cause of neuronal damage, evidence is accumulating that while in all instances abnormal levels of ICP increase the damage in at least some instances the elevation in ICP is a reflection of severe cellular damage rather than its cause.
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