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Head trauma Rodney S. Bagley DVM, Dipl.


(Neurology and Internal Medicine) Associate Professor, Washington State University College of Veterinary Medicine Pullman, Washington Traumatic injury remains a common cause of brain dysfunction in dogs and cats. Unfortunately, clinical studies regarding this type of brain injury are scarce and experimental studies, while often using animals as experimental subjects, lend more confusion than clarification to pathophysiology and treatment of traumatic brain injury. Much of the confusion arises because anecdotal information from non-controlled observations becomes accepted into management strategies and experimental studies usually focuses on a single aspect of traumatic brain injury while intracranial and systemic pathophysiological events associated with brain trauma are complex and interdependent. Many issues regarding management of traumatic brain disease remain controversial in cats as well as humans, and a consensus opinion on the most appropriate management of these injuries still does not exist. Pathophysiology of brain trauma Trauma to the brain can occur from exogenous or endogenous disease. Exogenous injury occurs most commonly from automobile trauma, although gun shot wounds and falls may also occur. Endogenous trauma can occur from neoplasia, inflammation, infection or vascular-related disease. All of these disease processes result in mechanical disruption of intracranial tissues (primary injury). This primary injury may initiate a number of secondary pathophysiological sequelae, such as metabolic alterations in neuronal or glial cells, impairment of vascular supply to normal tissue (ischemia), impairment of cerebrovascular autoregulation, hemorrhage (intraparenchymal, intraventricular, extradural or subdural), irritation (seizure generation), obstruction of the ventricular system, edema formation, production of physiologically active products, and finally, increased intracranial pressure (ICP). Selected important secondary pathophysiological disturbances are discussed below.1 Cerebral Edema Cerebral edema is a common sequela to brain trauma. maximal between 24 and 48 hours after acute injury.2 Brain edema becomes

Brain edema can be either cytotoxic, interstitial, or vasogenic.3 Cytotoxic (intracellular) edema results from failure of cellular energy processes with resultant failure of the sodium-potassium ATPase-dependent pump. This edema most often results from toxicity, ischemia, or hypoxia. Interstitial edema represents increased water content of the periventricular white matter due to movement of cerebrospinal fluid (CSF) across the ventricular walls in instances of hydrocephalus. Periventricular white matter is reduced due to the disappearance of myelin lipids caused by increases in white matter hydrostatic pressure.4 Vasogenic edema is the most common form of edema associated with intracranial neoplasia and other vascular-related injury. This type of edema occurs secondary to physical disruption of the vascular endothelium or functional alterations in endothelial tight junctions. Studies in rats have shown that blood vessels within brain tumors

have abnormal fenestrations, widened interendothelial junctions, increased pinocytic vesicles, infolding of luminal membranes, loosened and thickened basement membranes, or disrupted and widened extracellular spaces.5 Differences in transmural pressure gradients result in extravasation of fluid from cerebral vessels to the extracellular fluid spaces of the brain. 4 Areas if the brain where the extracellular space is normally expanded provide a natural conduit for fluid movement. Increases in intravascular pressure due to loss of autoregulation, vascular obstruction or hypertension (Cushing's response, cerebral ischemic response) may perpetuate edema formation. Vasogenic edema migrates away from areas of vascular disruption via bulk flow. 4 Fluid movement depends upon the balance between the opposing forces of capillary hydrostatic pressure and tissue resistance pressure. Vasogenic edema usually spreads through the white matter possibly because of the orderly arrangement of nerve fibers found there. This preferential involvement of white matter may be related to low capillary density and blood flow normally found there. The deep white matter of the cerebral hemispheres is commonly affected. Ischemia and Hypoxia Because normal function of neurons is primarily dependent upon an adequate supply of oxygen, physical disruption of blood flow to neurons can significantly impair normal function. Cerebral blood flow (CBF) is normally maintained via a combination of systemic blood flow and local cerebrovascular autoregulation. Trauma to the brain can disrupt cerebral vascular autoregulatory mechanisms leading to poor cerebral perfusion. Cerebral blood flow is normally dependent upon cerebral metabolic rate. Cerebral vessels, however, have the ability to alter their diameter in response to changes in PaCO2 (chemical autoregulation), as well as blood pressure (pressure autoregulation), in order to maintain a relatively constant CBF. With chemical autoregulation, cerebral vessels are directly influenced by PaCO 2 concentrations. As PaCO2 concentrations increase, cerebral vessels dilate to increase blood flow to the brain. The opposite effect is seen with decreased PaCO2. These cerebral vessels change diameter through alterations in perivascular pH. Autoregulation of CBF can also occur in response to systemic blood pressure changes in order to maintain a relatively constant CBF during both hypo- and hypertension.2 This prevents underperfusion, and subsequent ischemia, during times of hypotension and hemorrhage and edema during periods of hypertension. In most instances, CBF is maintained at a constant level when systemic blood pressure remains between 50 and 150 mm Hg. 2 Above and below these limits, CBF will be directly dependent upon systemic blood pressure. Cerebrovascular autoregulation is affected by a variety of intracranial processes. For example, local acidosis, common in many hypoxic and ischemic states, will disrupt local autoregulatory functions. If chemical autoregulation is absent in areas of diseased brain, hyperventilation will not alter vascular diameter in the affected area. In this instance, two situations are possible, both dependent upon the premise that cerebrovascular autoregulatory capacity is absent due to local disease. If local autoregulation is impaired and PaCO2 increases, vessels in surrounding normal brain will dilate. Vessels in the abnormal area are already maximally dilated due to loss of autoregulation. Vascular resistance will be decreased in surrounding

normal brain; blood will be shunted away from abnormal areas, potentially decreasing hemorrhage and edema, but resulting in further hypoxia (Steal Phenomenon).6 The opposite may occur as PaCO 2 is decreased by hyperventilation. Vessels in surrounding normal brain will vasoconstrict; vessels in the damaged or abnormal area of brain are already maximally dilated and are unable to constrict. Because of the vasoconstriction in normal brain, vascular resistance increases, shunting blood into the abnormal area (Inverse Steal or Robin Hood Phenomenon). 6 This has the positive effect of increasing cerebral blood flow to abnormal and potentially hypoxic areas of the brain, but may potentiate hemorrhage and cerebral edema in these areas due to the increased and excessive flow (luxury perfusion). The latter may contribute significantly to increased cerebral volume, increased ICP, and reperfusion injury. Unfortunately, whether local or global cerebrovascular autoregulation remains intact in brain injury is difficult to predict clinically. Global pressure autoregulatory function has been assessed in human patients with head injury and found to be intact in ~ 69% of head trauma patients. 7 Local loss of autoregulation, however, is almost impossible to predict in the clinical setting without sophisticated testing that is not practically available. It also appears, at least in the instance of external head trauma, that discrepancies can occur between pressure versus chemical (PaCO2-responsive) autoregulatory capacities.7 With head trauma, pressure autoregulation is often abnormal, whereas PaCO2-responsive autoregulation remains intact. This is termed dissociative vasoparalysis and has important ramifications during treatment. A more intimate control of systemic blood pressure is required to prevent large shifts of blood pressure and subsequent CBF. If pressure autoregulation is defective, significant increases in mean arterial blood pressure (MABP) will increase CBF and ultimately, ICP.7 If, on the other hand, pressure autoregulation is intact, decreased blood pressure will cause cerebrovascular vasodilatation increasing CBF and ultimately increasing ICP. All of these factors contribute to a myriad of intracranial blood flow alterations that can affect intracranial pressure and cerebral perfusion. Because chemical autoregulation often remains intact in head injury, however, hyperventilation may be a useful therapy to decrease PaCO 2, produce vasoconstriction, decreased CBF, and subsequently, decreased ICP (see therapy section). Hemorrhage Hemorrhage, either within or around the brain, may result in rapid cerebral dysfunction. The incidence of hemorrhage within or associated with intracranial trauma in cats is poorly documented. In an experimental study of blunt craniocerebral trauma in cats, all had some degree of subarachnoid hemorrhage, and many had subdural hemorrhage.8 Fifteen percent of these cats had subdural hematomas that displaced the corresponding cerebral hemisphere. Clinically significant subdural hematomas are however, uncommon in cats. Many of these experimentally traumatized cats also had cortical contusion. Intraparenchymal hemorrhage and petechiation were common, most often in the hemisphere directly receiving the blunt force. In some instances, hemorrhage extended into the subcortical white matter. This has significance as deep white matter hemorrhage increases the incidence of vasogenic edema. 9 One-fifth of the cats had tentorial herniation.

Hemorrhage into the cerebrospinal fluid results in inflammation, which may contribute to the clinical signs seen. Intraventricular hemorrhage, when primarily occurring in the third ventricle, can result in body temperature elevations, possibly due to temperature dysregulation in the diencephalon. Increased Intracranial Pressure Of the pathophysiological sequela associated with brain trauma, increases in ICP may be the most detrimental. Intracranial pressure/volume relationships are simply expressed by the Monro-Kellie doctrine. 10 This doctrine states that within the confines of the inelastic skull, blood, CSF and brain parenchyma normally exist in equilibrium, with each maintaining a relatively stable volume and pressure. Compensation for any increase in pressure or volume of one of these components must be equally and reciprocally accomplished by a decrease in one or both of the other components. If this does not occur, ICP will increase. Brain trauma alters this relationship by increasing intracranial volume via hemorrhage, edema, or changes in CBF. Cerebral hyperemia often accompanies cerebral trauma as a mechanism to increase blow flow to diseased brain. 11,12 Unfortunately, this increased cerebral blood flow increases intracranial volume and elevates ICP. Compensation for increased volume within the intracranial space will initially occur with minimal associated neuronal dysfunction. Mechanisms available for adaptation include shunting of CSF toward the lumbar cistern, decreasing CSF production, increasing CSF absorption, decreasing arterial blood flow, and increasing venous blood flow.13,14 Of these adaptive mechanisms, movements or shifts of CSF are the most effective in controlling increases in intracranial volume and pressure. Initially, the intracranial space is compliant to this increasing volume and no clinical signs associated with increasing ICP are seen. Clinical signs that are normally the result of increases in ICP may not be observed as ICP remains within the normal range. As intracranial tissues become less and less compliant, progressively smaller increases in volume now result in dramatic increases in ICP. Clinical signs resulting from increased ICP are noted, including mental status alterations, paresis, cranial nerve deficits, respiratory pattern alterations and compensatory systemic hypertension and bradycardia. Therapeutic intervention is often necessary to improve clinical signs and sustain neuronal function. As compliance is exhausted and intracranial volume continues to increase, shifts of brain parenchyma can occur which usually result in severe neurological impairment and death. Consequences of elevated ICP Shifts of brain parenchyma or brain herniation occur commonly with severe compartmentalized elevations in ICP. 15 Many of these are evidenced by the presence of mass effect on advanced imaging (computed tomography or magnetic resonance imaging) scans. When brain herniation occurs, even greater pressure is placed on vital brain structures, often resulting in death. Many types of brain herniation have been described including subfalcial, rostral and caudal transtentorial, and foramen magnum herniation. Transtentorial herniation may be evidenced by pupillary changes due to compression of the oculomotor nerve underneath the herniating cortex. If herniation is unilateral, the ipsilateral pupil will become dilated and unresponsive to light stimulation. Foramen magnum herniation usually results in impaired respiration due to pressure on respiratory centers in the caudal medulla.

Systemic effects When CBF decreases, the brain recognizes the ischemia and evokes a spectrum of physiological alterations known as the cerebral ischemic response. 16 These physiologic alterations are thought to emanate from vasomotor centers in the medulla oblongata. Failure of adequate blood flow to remove CO2 from receptors in these centers increases local CO2 concentrations which, in turn, stimulates the sympathetic nervous system to increase systemic blood pressure. Systemic hypertension results as an attempt to maintain cerebral blood flow. Baroreceptors within the systemic vasculature recognize this hypertension and relay this information to vagal centers also found in the medulla oblongata. The resultant increase in systemic vagal tone reflexly causes bradycardia. The systemic hypertension and associated reflex bradycardia is commonly referred to as Cushing's reflex and may explain why some cats with intracranial disease have bradycardia. Also, as ICP increases and cerebral perfusion pressure (CPP) subsequently decreases to a significantly low level, a large catecholamine release occurs. 17 This catecholamine release may result in myocardial ischemia known as brain-heart syndrome.17,18 Clinical arrhythmias are noted. Pathologically, focal myocardial ischemia is present, with focal white streaks seen grossly in the myocardium. 18 Histologically, myocardial degeneration is common. Brain-heart syndrome has been described in numerous species associated with intracranial and spinal lesions.18 Neurogenic pulmonary edema occurs due to a similar proposed mechanism. This edema occurs most commonly secondary to a seizure, and is thought to arise due to excessive sympathetic stimulation and alpha receptor-mediated vasoconstriction in the pulmonary vasculature.19 Such pulmonary edema is most commonly seen in the caudal dorsal lung fields. Respiratory abnormalities can occur with brain stem disease. The UMN respiratory centers are located in the pons and medulla oblongata of the brain stem. In the medulla there are dorsal and ventral respiratory nuclear groups that control respiration as well as a chemosensitive area that senses changes in CO2 concentration via the formation of hydrogen ions. Besides direct stimulation of the respiratory center, afferent information associated with respiration is projected to the respiratory center from the carotid bodies (chemoreceptors) through the glossopharyngeal nerve and then from aortic bodies through the vagus nerve. From these brain stem centers, the signal for respiration travels caudally to the cervical and cranial thoracic spinal cord to synapse on lower motor neurons (LMN) for respiration. These are found in the phrenic nerve (C4-C7 spinal segments), which innervates the diaphragm and the intercostal nerves (from the corresponding segmental spinal cord segments in the thoracic area) which innervate the intercostal muscles. There are a number of abnormal respiratory patterns seen with diseases of the nervous system. Cheyne Stokes respiration is characterized by waxing and waning depth of respiration with regularly occurring periods of hyperpnea and apnea. This is seen with bilateral cerebral or diencephalic disease. Biot’s breathing is irregular periods of apnea alternating with periods of 4 to 5 breaths of identical depth. This is seen with increased intracranial pressure.

Mesencephalic lesions may result in central neurogenic hyperventilation. Tachypnea to the point of panting is seen. Apneustic breathing occurs with pontine lesions and is characterized by periods of breathing and apnea that are very short. The cycles of respiration may consist of only one or two breaths interposed with periods of apnea. Caudal brain stem lesions involving the respiratory centers may cause irregular or ataxic breathing. Rostral cervical spinal cord lesions that interrupt the pathways between the brain stem respiratory centers and the LMNs needed for respiration may result in mechanical respiratory failure, dysphonia, and abdominal respiration where the abdomen moves out instead of in during inspiration.26 Diagnostic tests The diagnosis of trauma is usually straight-forward when the trauma is witnessed. In some instances, animals are presented with an acute onset of neurological signs and an unknown history. Examining for external signs of trauma such as lacerations or skull fractures is important. Evaluating the retinas and external ear canals for acute hemorrhage may also provide clues to the diagnosis. If head trauma is suspected, an initial neurological assessment followed by periodic evaluation (primarily to assess for secondary pathophysiological sequelae) is very important. At the time of the trauma, mechanical injury to the brain will have occurred resulting in the initial brain abnormalities. With secondary pathological sequelae, clinical signs may worsen, indicating the need for further diagnostics and therapy. Advanced imaging studies such as computed tomography (CT) or magnetic resonance (MR) imaging, are useful primarily for determining the need for surgical treatment. Surgical treatment centers around evacuation of subdural hematomas, removal of depressed skull fractures, or debridement of damaged tissue and foreign material. Surgical decompression may also be used as an adjunct treatment to stop increasing ICP (see below). Cerebrospinal fluid analysis is often unrewarding and may be detrimental, especially with elevated ICP. Withdrawal of CSF may alter intracranial fluid dynamics resulting in brain herniation.27 Therefore, unless a preexisting disease is suspected prior to the trauma, it is best to avoid CSF collection. Electrophysiological evaluations such as brain stem auditory evoked potentials (BSEP) and electroencephalography (EEG) have the potential to provide localization as well as prognostic information. Often however, these tests yield nonspecific information, and results may not correlate with recovery.28 Also, baseline data in the individual animal is usually not available for comparison and therefore, it is difficult to know if the abnormalities seen reflect prior disease or are associated with the traumatic incident itself. Survey radiographs of the skull may aid in determining whether fractures are present. This information may allow for assumptions about underlying brain injury, but does not determine the extent of that injury. Cervical spinal radiographs should be included to rule out a cranial cervical lesion that may result in clinical signs similar to a caudal brain stem lesion. Monitoring

From a practical standpoint, monitoring for and treatment of the secondary effects of craniocerebral trauma may be the most important things performed in daily clinical practice. Recognition, understanding, and treatment of the secondary pathophysiological sequelae of brain injury often impact more on prognosis than does the initial injury. After suspected intracranial trauma, life-threatening systemic complications should be recognized and treated. Initial neurological assessments should be recorded, although critical assessments of neurological impairment can most accurately be made only after stabilization of systemic abnormalities. As complete a neurological evaluation should be made at this time, and recorded for further comparisons. Many animals are remarkably improved within 24 hours of head trauma. A coma scale is used as a guide to determining treatment and prognosis in humans with brain injury. 29 A similar scale has been adapted for use in dogs; however, its role in determining treatment and prognosis is less clear. 30 A common sense approach based upon diligent and repeated assessment of major neurological functions, such as level of consciousness and voluntary movement, is usually most important. Fluid administration should be critically monitored, as overhydration with isotonic fluids may perpetuate brain edema.31 Monitoring of systemic blood pressure and central venous pressure may aid in re-establishment of normovolemia. Implantation of a central venous catheter should be performed cautiously in an animal with increased ICP, as manipulation or occlusion of the jugular vein for catheter placement may elevate ICP. Quick, efficient, and atraumatic jugular catheterization is a must in this situation. After the initial neurological assessment, a decision should be made as to whether an advanced imaging study (CT or MR) is indicated to determine if additional treatments are necessary. If these studies are unavailable or not feasible, or if the clinical signs are mild, the animal should be periodically monitored (hourly, if necessary) for deteriorating neurological function. If clinical signs are severe from the onset, or worsen progressively, ICP should be measured and if elevated, treated appropriately. If ICP monitoring is not available or feasible, treatment for elevated ICP should be based upon clinical signs. Measurement of ICP Intracranial pressure is thought to equilibrate equally within and among the intracranial contents, although local increases in ICP have been noted. Measurement of ICP ipsilateral to a unilateral lesion most accurately reflects pathologically increased ICP. 32 Attempts to measure ICP have however, most commonly relied upon measurement of CSF pressure via needle puncture at either the cerebellomedullary cistern or the lumbar subarachnoid space. A manometer is attached to the needle hub and the pressures are recorded in centimeters of water. Unfortunately, this technique incorporating only a single time measurement is often of little diagnostic and therapeutic value as ICP changes are frequently episodic. This method also discounts compartmentalized ICP changes that can occur secondary to herniation. For more chronic measurement of ICP, a fiberoptic ICP monitoring system has been utilized in humans.33,34 This method of ICP measurement has now been adapted for use in dogs and cats.35

In this technique, a fiberoptic transducer is surgically introduced into either the epidural, subdural, intraparenchymal or intraventricular spaces through a small hole in the skull. The catheter is most often placed into the cortical parenchyma, ideally on the side of the most severe lesion. If a unilateral intracranial lesion exists that requires surgery, the catheter is placed in the hemisphere opposite to the proposed craniotomy. Pressures can be recorded continually for hours to days. While this device has not commonly been used in cats for chronic monitoring outside the operating room, it has often been used in non-anesthetized humans with head trauma for monitoring of ICP as a guide for therapeutic intervention. Intracranial pressures using this system have been determined in clinically normal dog and cats under isoflurane anesthesia. 35 Mean pressures range from 8 - 15 mm Hg with a mean of 11-12 mm Hg for both groups.36-40 An absolute level of ICP however, that constitutes pathologically elevated ICP has not been established in animals or man. In humans, absolute ICP greater than 15 - 20 mm Hg is usually treated. Similar guidelines have not been established for cats. Nevertheless, it would seem reasonable to follow the recommendations used in humans. As with the use of all ICP monitoring systems, a trend toward increasing ICP above normal ranges may be more important than the absolute measured ICP. Treatment Maintenance of systemic function Basic life support measures may be necessary including blood or isotonic fluid administration. Common critical care protocols should be followed with the following considerations when head trauma is a component of the injury. Corticosteroids Corticosteroid use in head trauma is widespread and often based upon anecdotal evidence of efficacy. The role of methylprednisolone sodium succinate in spinal trauma is widely accepted and scientifically defensible. Beneficial effects of methylprednisolone in nervous system injury include inhibition of lipid peroxidation and its associated detrimental effects.41 The role of corticosteroids in the treatment of head trauma however, is unclear. One study has shown that methylprednisolone has benefited rats with head trauma, while others have shown no benefit in clinically affected humans.41-43 The concerning aspects of corticosteroid use center around the potential detrimental role of corticosteroids to the nervous system when neuronal ischemia is present, as well as the other established gastrointestinal side effects of the drug.44,45 It is known that corticosteroids potentiate ischemic injury to neurons.44 It is not established whether this is due to direct toxic effects of corticosteroids or due to secondarily induced metabolic derangements. It is also established that humans that are hyperglycemic at the time of head trauma have a worse overall prognosis than people who are normoglycemic.46 The increased concentrations of glucose in anaerobic brain tissue associated with ischemia may potentiate lactic acid accumulation and increase neuronal damage. Considering that severe head trauma is most likely associated with some degree of cerebral ischemia and that corticosteroids can result in a short-term increase in blood glucose, these same detrimental affects may apply when exogenous corticosteroids are used for treating brain trauma. Whether corticosteroid use is beneficial or detrimental in head trauma however, must await further experimental study.

Head Elevation Head elevation to 30o above heart level will decrease ICP primarily by facilitating venous drainage. 47 There is debate concerning this therapy with opponents suggesting that head elevation may decrease cerebral perfusion and therefore be detrimental to brain function. A recent study in humans however, has shown that cerebral perfusion pressure and cerebral blood flow is maintained in the 30 o head elevation position as ICP is concurrently decreased. 47 Reduction of ICP with this relatively simple treatment may be beneficial in combination with other ICP decreasing measures in cats.

Hyperventilation Hyperventilation can decrease ICP due to the established effects of PaCO 2 concentrations on cerebral blood flow. As stated earlier, cerebral vessels are directly responsive to PaCO2 concentrations.2 If autoregulation is intact, hyperventilation to decrease PaCO2 will cause cerebral vasoconstriction, decreased cerebral blood volume, and subsequently decreased ICP. Hyperventilation in this instance should be used to maintain PaCO 2 between 28 and 32mm Hg to avoid cerebral hypoxia from poor ventilation, which will also be detrimental to neuronal survival. Endotracheal intubation and ventilator support can be performed under the influence of barbiturate anesthesia or neuromuscular blockade. Appropriate ventilator management is imperative. Diuretics Mannitol As cerebral edema contributes to intracranial volume and subsequently, increases in ICP, treatments that decrease cerebral edema are often used to lower ICP. Mannitol is the most commonly used diuretic in clinical practice to decrease cerebral edema and ICP. Mannitol has been thought to decrease cerebral edema primarily through its associated osmotic effects, although other effects, such as concurrent decreases in blood viscosity and free radical scavenging, may in fact, be more beneficial. 48 By decreasing blood viscosity, cerebral perfusion will be increased at the same level of systemic blood pressure. Vasoconstriction will result, lowering cerebral blood volume and concurrently lowering ICP. While mannitol may decrease peritumoral edema, its antiedema effects may be more effective in reducing the water content in more normal brain compared to pathological brain. Mannitol is administered at 1 grams/kg, IV, over 5 to 10 minutes. Maximal lowering of ICP most often occurs in 10 to 20 minutes. In both humans and dogs with normal ICP, mannitol infusion is associated with an initial, short-lived increase in ICP. 49,50 If ICP is elevated prior to treatment, ICP decreases consistently. 48-53 Therefore, mannitol appears more effective in patients who have increased ICP wherein precipitous decreases in ICP are seen. In patients where ICP is normal, the effect of mannitol on lowering ICP is less dramatic.

Contraindications to mannitol use include hypovolemia and ongoing intracranial hemorrhage. Mannitol has also been shown to induce histamine release from basophils, which may result in hypotension and a shock-like state. 54 Additionally, after the initial decrease in ICP from mannitol administration, ICP may increase (rebound) back to similar or even higher levels than even before its administration. 49 A decrease in fluid intake and subsequently, an increase in vascular viscosity may be responsible. Sludging of cerebral blood flow then results in vasodilation of cerebral vessels, increased cerebral blood volume and subsequently, increased ICP. Preventing dehydration in the post-mannitol administration period may decrease this potential secondary complication.49 Furosemide Furosemide (0.7 mg/kg IV) is a loop diuretic that may help to lower ICP primarily, or may potentiate the effects of mannitol. Furosemide is given as a preoperative diuretic in humans undergoing craniotomy lowered ICP comparably to mannitol.55 Additionally, furosemide did not result in an initial increase in ICP as with mannitol. Furosemide given 15 minutes after mannitol administration potentiates the intracranial pressure-lowering effects of the latter.56 Other hypertonic solutions, such as dextrose and albumin, appear to be less effective at lowering ICP as compared to mannitol and furosemide.57 This may be the result of these latter solutions being more freely diffusible across cell membranes with a resultant inability to establish a quantitatively significant osmotic gradient for fluid movement. Cerebrospinal Fluid Aspiration Cerebrospinal fluid aspiration is sometimes used as the initial means to decrease ICP.58 This is most helpful in humans if a ventriculostomy is present and if ICP elevations do not exceed 30 mm Hg. The use of a CSF tap alone is not recommended in animals with suspected increased ICP however, due to the increased risk of precipitating brain herniation. Barbiturates Barbiturates (pentobarbital 3 mg/kg IV to effect) can be used to induce coma thereby decreasing cerebral metabolism, cerebral blood flow, and subsequently ICP. 59 Barbiturates may benefit brain blood flow by causing vasoconstriction in normal tissue and shunting blood to ischemic areas. Other suggested benefits include decreases in vasogenic edema, oxygen metabolism, intracellular calcium, and increases in free radical scavenging. 59 Pentobarbital is usually administered as a constant intravenous infusion in order to achieve and maintain a burst-suppression pattern on the electroencephalogram. 59 Arterial blood pressure should be monitored closely, as barbiturates can result in hypotension, which may decrease cerebral blood flow and increase cerebral ischemia. Beneficial effects from barbiturate coma in humans with intracranial pressure elevations have been variable. Similar to other treatments, success should be assessed based not only on the ability of the treatment to lower ICP, but also on the ultimate degree of functional recovery. Barbiturate therapy may however, be more

beneficial for patients with brain trauma who have preserved cerebrovascular reactivity to changes in PaCO2 than those who do not. Hypothermia Hypothermia has been used experimentally in dogs and clinically in humans to decrease ICP when other treatments are less effective. 60-62 It is not been used in cats. Cooling of the body may prevent the ischemia-induced release of excitatory neurotransmitters such as glutamate. 60 This decrease in extracellular levels of the excitatory neurotransmitters may prevent the rapid influx of extracellular calcium into the cell which leads to free radical production and eventually, cell death. Conventional hypothermia, where the core body temperature is lowered to < 30oC, decreases cerebral metabolic rate and may lessen cerebral edema.61 Cooling to this level however, has been associated with unfavorable outcomes and cardiovascular instability. Milder degrees of hypothermia (core body temperature at 31 - 35oC) are currently being used. While ICP is decreased, morbidity and mortality, especially during rewarming, are persistent concerns as the risk of brain herniation is present. Further studies however, may support the use of hypothermia as an adjunct therapy for elevated ICP. Miscellaneous Drugs Other drugs have been suggested as potential adjunctive therapies in brain injury, although clinical studies to support experimental information, is less readily available. The antioxidant drug, deferoxamine mesylate has been shown to reduce coldinduced brain edema in cats.63 Other drugs under investigation for use in brain injury include superoxide dismutase, allopurinol, opiate antagonists (naloxone), thyrotropin-releasing hormone, and calcium channel blockers.64 Future clinical trials in naturally occurring head trauma in cats are needed to determine their efficacy. Anesthesia Anesthesia may be necessary for diagnostic testing or surgery. As many anesthetic agents have the potential to worsen neurological disease, anesthesia protocols should be used in light of their effects on intracranial physiology. Anesthetic agents that can be used in brain injured animals have been reviewed elsewhere, 65-71 although isoflurane is currently a reasonably safe inhalation agent which has little effect on cerebral blood flow autoregulation.72 Craniotomy A major tenet of the Monro-Kellie doctrine is that intracranial contents are confined within the cranium. It would follow therefore, that surgical removal of this structure would potentially relieve ICP elevations. Unilateral or bilateral craniectomy has been used as a treatment for ICP elevations that cannot be decreased by the more conventional methods stated above. 35,37,73-77 While skull removal alone may be beneficial, subsequent dural incision appears significantly more effective in lowering ICP. This has been shown clinically in humans, and experimentally in dogs, as well as cats.35,37,73-77 Ultimate functional recovery remains dependent upon the underlying primary brain damage inflicted by the disease process. Because ICP may

increase during wound closure and anesthetic recovery, the magnitude of ICP decrease subsequent to surgery nevertheless, remains uncertain. Craniectomy and durotomy has been shown to lower ICP by 15 and 65 % respectively in dogs, cats, and humans. 35,37,75 Intracranial pressures in normal dogs approached atmospheric pressure when a lateral rostrotentorial craniectomy and durotomy were performed. Adequate decompression of the brain in animals with structural disease would be suggested if intraoperative ICP approached similar levels. Rehabilitation of the brain injured animal In general, lesions of supratentorial structures or the cerebellum have a better overall prognosis for recovery than lesions involving the brain stem. After the acute effects of brain injury are controlled (usually within 7 days), the goal is to allow time for brain healing and recovery of function to occur. Smaller animals are often better candidates for prolonged nursing care in comparison to larger animals due to the relative ease of physical manipulation. Good nursing care includes the prevention of decubital ulcers in the recumbent animal and monitoring for secondary infections primarily of the pulmonary and urogenital systems. Recumbent animals should be placed on clean, soft bedding and turned frequently (at least every 4 hours). Physical therapy can begin as soon as possible if there are no unstable vertebral injuries. Physical therapy is individualized to the animal's needs, but may include supported or non-supported walking, passive flexion and extension of the limbs, massage, or swimming. Cats may be more reluctant than dogs to perform the latter physiotherapy. A daily record of physical therapy will ensure that this therapy is not overlooked, and allows for multiple individuals, including the owner, to become involved in the healing process. In general, clinical signs of unilateral supratentorial injury improve within the first two weeks following trauma. Usually the animal is ambulatory by 4 weeks post injury although residual paresis and blindness may continue. A tendency to circle may also persist, being especially prominent when the animal is distressed or excited. Recovery from brain stem injury may be less complete, and residual signs commonly remain. Recovery from cerebellar injury often occurs in a similar time frame as for supratentorial injury. If the secondary effects of brain injury are controlled, many animals can recover from the primary brain insult associated with trauma.

References 1. Bagley RS. Pathophysiological effects of central nervous system tumor. Proceeding of the Twelfth Annual Veterinary Medical Forum, Washington, DC, May 1994, 928-930 2. Shapiro HM. Intracranial hypertension. Therapeutic and anesthetic considerations. Anesthesiology 43:445-471, 1975. 3. Fishman RA. Brain edema. N Eng J Med 293:706-711, 1975. 4. Reulen HJ. Vasogenic Brain Oedema: New aspects in its formation, resolution and therapy. Br J Anaesth 48:741-752, 1976. 5. Nishio S, Ohta M, Abe M, Kitamura K:Micorvascular abnormalities in ethylnitrosourea (ENU)-induced rat brain tumors:Structural basis for altered bloodbrain-barrier function. Acta Neuropathol (Berl) 59:1-10, 1983. 6. Enevoldsen EM, Jensen FT. Autoregulation and CO2 responses of cerebral blood flow in patients with acute severe head injury. J Neurosurg 48:689-703, 1979. 7. Bouma GJ, Muizelaar JP, Bandoh K, Marmarou A. Blood pressure and intracranial pressure-volume dynamics in severe head injury: relationship with cerebral blood flow. J Neurosurg 77:15-19, 1992. 8. Tornheim PA, Liwnicz BH, Hirsch CS, Brown DL, McLaurin RL. Acute responses to blunt head trauma. J Neurosurg 59:431-438, 1983. 9. Tornheim PA, McLaurin RL, Thorpe JF. The edema of cerebral contusion. Surg Neurol 5:171-175, 1976. 10. Kornegay JN. Pathogenesis of diseases of the central nervous system. In Textbook of Small Animal Surgery, 2nd ed., Slatter D, ed., Philadelphia, W.B. Saunders, 1993, 1022-1037. 11. Lobato RD, Sarabia R, Cordobes F, Rivas JJ, et al. Posttraumatic cerebral hemispheric swelling. J Neurosurg 68:417-423, 1988. 12. Orbrist WD, Langfitt TW, Jaggi JL, Cruz J, et al. Cerebral blood flow and metabolism in comatose patients with acute head injury. J Neurosurg 61:241-253, 1984. 13. Lyons MK, Meyer FB. Cerebrospinal fluid physiology and the management of increased intracranial pressure. Mayo Clinic Proc 65:684-707, 1990. 14. Germon K. Interpretation of ICP pulse waves to determine intracerebral compliance. J Neurosci Nurs 20:344-349, 1988. 15. Kornegay JN, Oliver JE, Gorgacz EJ. Clinicopathologic features of brain herniation in animals. J Am Vet Med Assoc 182:1111-1116, 1983. 16. Guyton AC: Arterial pressure regulation:I. Rapid pressure control, In Textbook of Medical Physiology, 7th ed,Philadelphia, W.B. Saunders, 1986, pp 250-251.

17. van Loon J, Shivalkar B, Plets C, Goffin J, et al. Catecholamine response to a gradual increase of intracranial pressure. J Neurosurg 79:705-709, 1993. 18. King JM, Roth L, Haschek WM: Myocardial necrosis secondary to neural lesions in domestic animals. J Am Vet Med Assoc 180:144-148, 1982. 19. Lagerkranser M, Pehrsson, Sylvén C. Neurogenic pulmonary oedema. Acta Med Scand 121:267-271, 1982 20. Braund KG:Clinical Syndromes in Veterinary Neurology. 2nd edn. St. Louis: Mosby. 1994. 21. deLahunta, A : Veterinary Neuroanatomy and Clinical Neurology, 2nd edn. Philadelphia:WB Saunders, 1983. 22. Chrisman CL. Problems in Small Animal Neurology, 2nd edn. Philadelphia:Lea & Febiger. 1991. 23. Oliver JE, Hoerlein BF, Mayhew IG: Veterinary Neurology, , Philadelphia:WB Saunders 1987. 24. Oliver JE Jr, Lorenz MD: Handbook of Veterinary Neurologic Diagnosis, Philadelphia:WB Saunders. 1993. 25. Wheeler S J. Manual of Small Animal Neurology, West Sussex:British Small Animal Veterinary Association. 1995. 26. Bagley RS, Stefanacci JD, Hansen B, Kornegay JN. Dysphonia in two dogs with cranial cervical intervertebral disk extrusion. JAAHA 29:557-559, 1993. 27. Duffy GP. Lumbar puncture in the presence of raised intracranial pressure. Br Med J 1:407-409, 1969. 28. Schoenhuber R, Gentilini M, Orlando A. Prognostic value of auditory brain-stem responses for late postconcussion symptoms following minor head injury. J Neurosrug 68:742-744, 1988. 29. Pal J, Brown R, Fleiszer D. The value of the Glasgow coma scale and injury severity score:Predicting outcome in multiple trauma patients with head injury, J of Trauma 29:746-748, 1989. 30. Shores A. Craniocerebral trauma. In Kirk RW, ed, Current Veterinary Therapy, 10th ed, Philadelphia, W.B.Saunders, 1989, 847-853. 31. Hariri RJ, Firlick AD, Shepard SR, Cohen DS, et al. Traumatic brain injury, hemorrhagic shock, and fluid resuscitation:effects on intracranial pressure and brain compliance. J Neurosurg 79:421-427, 1993. 32. Weaver DD, Winn HR, Jane JA. Differential intracranial pressure in patients with unilateral mass lesions. J Neurosurg 56:660-665, 1982. 33. Crutchfield JS, Narayan RK, Robertson CS, Michael LH. Evaluation of a fiberoptic intracranial pressure monitor. J Neurosurg 72:482-487, 1990.

34. Artru F, Terrier A, Gibert I, Messaoudi K, et al. Monitorage de la pression intracrânienne par capteur intraparenchymateux à fibres optiques: Aspects techniques et fiabilité clinique. Ann Fr Anesth Réanim 11:424-429, 1992. 35. Harrington ML, Bagley RS, Moore MP, Keegan RD, Baszler TV. Effect of craniectomy on intracranial pressure in normal cats. (unpublished observations). 36. Bagley RS, Baszler TV, Harrington ML, Pluhar GE, Moore MP, Keegan RD, Greene SA. Clinical effects of longitudinal division of the corpus callosum in dogs. Vet Surg 24:122-127, 1995. 37. Bagley RS, Harrington ML, Pluhar GE, Keegan RD, Greene SA, Moore MP, Gavin PR: The effect of combination hyperventilation, diuretics, corticosteroids and craniectomy/durotomy versus craniectomy/durotomy alone of intracranial pressure in normal dogs. Am J Vet Res 57:116-119, 1996. 38. Bagley RS, Keegan RD, Greene SA, Harrington ML, Moore MP: Pathological effects in brain following intracranial pressure monitoring in normal dogs using a fiberoptic monitoring system. Am J Vet Res 56:1475-1478, 1995. 39. Keegan RD, Greene SA, Bagley RS, Moore MP, Weil AB, Short CE. Effects of medetomidine administration on intracranial pressure and cardiovascular variables of isoflurane anesthetized dogs. Am J Vet Res 1995. 40. Pluhar GE, Bagley RS, Keegan RD, Moore MP: The effect of acute, unilateral transverse venous sinus occlusion on intracranial pressure in normal beagles. Vet Surg 23:425, 1994. 41. Hall ED. The neuroprotective pharmacology of methylprednisolone. J Neurosurg 76:13-22, 1992. 42. Hall ED. High-dose glucocorticoid treatment improves neurological recovery in head-injured mice. J Neurosurg 62:882-887, 1985. 43. Braakman R, Schouten HJA, Dishoeck MB, Minderhound JM. Megadose steroid in severe head injury. J Neurosurg 58:326-330, 1983. 44. Sapolsky RM, Pulsinelli WA. Glucocorticoids potentiate ischemic injury to neurons: Therapeutic implications. Science 229:1397-1400, 1985. 45. Toombs JP, Collins LG, Graves GM, Crowe DT, Caywood DD. Colonic perforation in corticosteroid-treated dogs. JAVMA 188:145-150, 1986. 46. Lam AM, Winn HR, Cullen BF, Sundling N. Hyperglycemia and neurological outcome in patients with head injury. J Neurosurg 75:545-551, 1991. 47. Feldman Z, Kanter MJ, Robertson CS, Contant CF, et al. Effect of head elevation on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in head-injured patients. J Neurosurg 76:207-211, 1992. 48. Ravussin P, Archer DP, Tyler JL, Meyer E, et al. Effects of rapid mannitol infusion on cerebral blood volume. J Neurosurg 64:104-113, 1986.

49. Ravussin P, Archer DP, Meyer E, Abou-Madi M, et al. The effects of rapid infusions of saline and mannitol on cerebral blood volume and intracranial pressure in dogs. Can Anaesth Soc J 32:506-515, 1985. 50. Ravussin P, Abou-Madi M, Archer D, Chiolero R, et al. Changes in CSF pressure after mannitol in patients with and without elevated CSF pressure. J Neurosurg 69:869-876, 1988. 51. Mendelow AD, Teasdale GM, Russell T, Flood J, et al. Effect of mannitol on cerebral blood flow and cerebral perfusion pressure in human head injury. J Neurosurg 63:43-48, 1985. 52. Shackford SR, Zhuang J, Schmoker J. Intravenous fluid tonicity: effect on intracranial pressure, cerebral blood flow, and cerebral oxygen delivery in focal brain injury. J Neurosurg 76:91-98, 1992. 53. Abou-Madi M, Trop D, Abou-Madi N, Ravussin P. Does a bolus of mannitol initially aggravate intracranial hypertension. Br J Anaesth 59:630-639, 1987. 54. Findlay SR, Dvorak AM, Kagey-Sobotka A, Lichtenstein LM. Hyperosmolar triggering of histamine release from human basophils. J Clin Invest 67:1604-1613, 1981. 55. Cottrell JE, Robustelli A, Post K, Turndorf H. Furosemide- and mannitol-induced changes in intracranial pressure and serum osmolality and electrolytes. Anesthesiology 47:28-30,1977. 56. Roberts PA, Pollay M, Engles C, Pendleton B, et al. Effect of intracranial pressure of furosemide combined with varying doses and administration rates of mannitol. J Neurosurg 66:440-446, 1987. 57. Albright AL, Latchaw RE, Robinson AG. Intracranial and systemic effects of osmotic and oncotic therapy in experimental cerebral edema. J Neurosurg 60:481489, 1984. 58. Lyons MK, Meyer FB. Cerebrospinal fluid physiology and the management of increased intracranial pressure. Mayo Clinic Proc 65:684-707, 1990. 59. Nordström CH, Messeter K, Sundbärg G, Schalén W, et al. Cerebral blood flow, vasoreactivity, and oxygen consumption during barbiturate therapy in severe traumatic brain lesions. J Neurosurg 64:231-237, 1986. 60. Marion DW, Obrist WD, Carlier PM, Penrod LE, et al. The use of moderate therapeutic hypothermia for patients with severe head injuries: a preliminary report. J Neursurg 79:354-362, 1993. 61. Pomeranz S, Safar P, Radovsky A, Tisherman SA, et al. The effect of resuscitative moderate hypothermia following epidural brain compression on cerebral damage in a canine outcome model. J Neurosurg 79:241-251, 1993 62. Shiozaki T, Sugimoto H, Taneda M, Yoshida H, et al. Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg 79:363-368, 1993.

63. Ikeda Y, Ikeda K, Long DM. Protective effect of the iron chelator deferoxamine on cold-induced brain edema. J Neurosurg 71:233-238, 1989. 64. Dewey CW, Budsberg SC, Oliver Jr JE. Principles of head trauma management in dogs and cats - Part II. Comp Contin Ed 15:177-193, 1993. 65. Shores A. Neuroanesthesia:A review of the effects of anesthetic agents on cerebral blood flow and intracranial pressure in the dog. Vet Surg 14:257-263, 1985. 66. Cornick JL. Anesthetic management of patients with neurologic abnormalities. Comp Contin Ed Pract Vet 14:163-172, 1992 67. Adams RW, Cucchiara RF, Gronet GA, Messick JM, Michenfelder JD. Isoflurane and cerebrospinal fluid pressure in neurosurgical patients. Anesthesiology 54:97-99, 1981 68. Grosslight K, Foster R, Colohan AR, Bedford RF. Isoflurane for Neuroanesthesia:Risk factors for increases in intracranial pressure. Anesthesiology 63:533-536, 1985 69. Fenner WR. Neuroanesthesia. Proceedings of the Tenth Annual Veterinary Medical Forum, San Diego, CA, May 1992, 722-724. 70. Drummond JC, Todd MM. The response of the feline cerebral circulation to PaCO2 during anesthesia with isoflurane and halothane and during sedation with nitrous oxide. Anesthesiology 62:268-273, 1985. 71. Todd MM, Drummond JC. A comparison of the cerebrovascular and metabolic effects of halothane and isoflurane in the cat. Anesthesiology 60:276-282, 1984. 72. Drummond JC, Todd MM, Shapiro HM. Cerebral blood flow autoregulation in the cat during anesthesia with halothane and isoflurane. Anesthesiology 59:A305, 1983. 73. Venes Jl, Collins WF. Bifrontal decompressive craniectomy in the management of head trauma. J Neurosurg 42:429-433, 1975 74. Fisher CM, Ojemann RG. Bilateral decompressive craniectomy for worsening coma in acute subarachnoid hemorrhage. Observations in support of the procedure. Surg Neurol 41:65-74, 1994 75. Jourdan C, Convert J, Mottolese C, Bachour E, Gharbi S, Artru F. [Evaluation of the clinical benefit of decompression hemicraniectomy in intracranial hypertension not controlled by medical treatment]. Neuro Chirurgie 39:304-310, 1993. 76. Gaab MR, Rittierodt M, Lorenz M, Heissler HE. Traumatic brain swelling and operative decompression: a prospective investigation. Acta Neurochirurgica Suppl 51:326-328, 1990. 77. Rinaldi A, Mangiola A, Anile C, Maira G, Amante P, Ferraresi A. Hemodynamic effects of decompressive craniectomy in cold induced brain oedema. Acta Neurochirurgica Suppl 51:394-396, 1990. Footnotes

aOlm Intracranial Pressure Monitoring Kit- Model 110-4B. Camino Laboratories, San Diego, California bDigital Pressure Monitor, Model 420, Camino Laboratories, San Diego, California