PATHOPHYSIOLOGY OF RAISED INTRACRANIAL PRESSURE.

The Monroe-Kellie doctrine states that the skull is a rigid cavity and that its contents are relatively noncompressible and consist of the brain parenchyma, intravascular blood, and cerebrospinal fluid. Expansion in the volume of any one compartment is likely to occur at the expense of the other two (e.g., an increase in the volume of the brain perenchyma because of a neoplasm is compensated for by the expression of cerebrospinal fluid out of the brain compartment into the spinal subarachnoid space and a decrease in blood volume because of compression of the dural venous sinuses). Because each compartment is relatively noncompressible, its volume is directly proportional to its intrinsic pressure. The global ICP represents the sum of the partial pressure of the individual compartments. Although the Monroe-Kelli doctrine is a useful concept, it is not as consistently applicable to infants as it is to adults. This is due to the inherent give or compressibility of the brain parenchyma, since a neoplasm can expand locally in the relatively unmyelinated brain of the infant, exerting localized pressures that are not uniformly transmitted to the entire brain. Also, the cranial cavity is not a rigid container in infants, since it can enlarge after splitting of the cranial sutures. The pressure volume relationships in the brain may be described by following equation:

C= dV/dp

where C represents compliance and dV represents the change in volume that accompanies a change in pressure (dp). Compliance is the ability of the brain to accommodate increase in intracranial volume without changes in ICP. It follows a hyperbolic curve (figure 60-1). As ICP rises, compliance decreases. Along the horizontal segment of the curve, increases in intracranial volume will raise the pressure only slightly beacause compensatory mechanisms main-train a physiologic state. Beyond a certain point, however, ever minor increases in volume lead to disproportionately greater increases in ICP. In the h healthy brain, compliance is along the horizontal segment of the curve, whereas in a swollen, damaged brain, compliance is located along the vertical segment of the curve. The overall slope of the pressurevolume curve is steeper in infancy than in older children (Figure 60-1). An increase in intracranial volume by 10 ml is not likely to cause as much of an increase in ICP in an adolescent as in an infant. This steeper volum-pressure curve persist in infancy until the point of separastion of the cranial sutures. Thereafter the infant's cranial cavity is able to accommodate relatively more volume than the adult skull. Patients with craniosynostosis (premature closure of the sutures) are at risk for increased ICP because of an inability of the sutures to separate, as well as from insufficient space within the calvarium for the accommodation of normal brain growth. Brain edema occurs consintently in patients with increased ICP. It can be vasogenic, cytotoxic, or hydrostatic in nature. Vasogenic cerebral edema is related to opening of the tight juntions in the blood-

brain capillaries and transudation of fluid into the extracellular space. It is commonly observed in head trauma, neoplasm, inflammatory disorders, and lead encephalopathy and is responsive to glucocorticoids. Diffusion-weighted magnetic resonance imaging reveals increased signal intensities in the T2 sequences in patient with vasogenic edema, thus helping to differentiate it from cytotoxic brain edema. Endothelial damage triggered by the local release of cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 histamine and arachidonic acid may play a role in its development. Cytotoxic edema results from processes, usually toxic or metabolic, that affect the cell membranes of neurons and glial cells so that they are unable to maintain a stable pump mechanism and internal milieu, leading to hydropic swelling. It commonly occurs during hypoxic-ischemic encephalopathy and is not steroid-responsive. Interstitial edema is characterized by transependymal transudation of crebrospinal fluid into the adjacent white matter and is generally seen in patients with hydrocephalus. The various forms of edema are not mutually exclusive and may coexist to varying degress.

Impact on cerebral perfusion.

The normal cerebral blood flow rate in newborns is about 40 ml/100g/minute and 53 ml/100 g/minute in older children and adults (shapiro,1994). Increased ICP reduces cerebral blood flow. The primary objective in controlling brain swelling is therefore the prevention of brain ischemia (Leursen, 1997). This relationship between ICP and blood flow is best expressed by the following equations:

CPP = SAP ICP

CPP= [(SAP+2DAP)/3]-ICP

Where: CPP= Cerebral perfusion pressure SAP= systemic arterial pressure DAP= Diastolic arterial pressure

The normal cerebral perfusion pressure is between 50 to 55 mm of Hg. The physiologic cerebral

perfusion pressure might be lower in children because of lower values of the systemic arterial pressure and ICP. A drop below 50 mm is generally associated with ischemic brain injury. When cerebral perfusion pressure decreases to 40% of normal, electrophysiologic function in the brain fails, and neuronal ischemia and death ensue (trauner, 1989). This underscores the importance of avoiding hypotension in any subject with increased ICP from fluid restriction or overzealous use of volumedepleting, hyperosmolar agents. Autoregulation is the ability of the brain to maintain stable blood flow in the face of fluctuations in the cerebral perfusion pressure , which is accomplished via regional vasoconstriction or vasodilatation. Autoregulation is frequently compromised in patients with raised ICP, and this creates a pressurepassive system wherein systemic hypotension can provoke aditional ischemic injury. The mediators of metabolic autoregulation are changes in tissue Ph, potassium ions .The cerebral vasculature is also responsive to changes in arterial oxygen and carbon dioxide tension, Small fluctuations in Pao2 do not alter cerebral blood flow, but there is an inverse relationship between cerebral blood flow and oxygen tension when the Pao2, drops below 50 torr, with a threefold increase in cerebral blood flow by the time Pao2, drops to 20 t0 25 torr. The vascular response to changes in paco2, is even more sensitive. For each 1 torr change in paco2 CBF changes in the same direction by 3% to 4%. The lower limit for this response is about 20 torr in adults and about 15 torr in children. When compliance is impaired and shifted to the steep segment of the pressure- volume curve, autoregulation is also impaired and even minor increases in cerebral blood flow lead to significant rises in ICP.

INTRACRANIAL PRESSURE MONITORING RATIONALE.

Increased ICP is dificult to verify on clinical grounds alone. Also the yield of the clinical examination may be compromised by sedative agents or skeletal muscle paralytic agents that have been administered for the respiratory management of the comatose patient. The objective should be recognizing and alleviating intracranial hypertension before it leads to irreparable brain damage. The decision to monitor ICP in any given patient is based on the premise that the ICP elevation is going to be sustained for some period of time (more than a few hours). It should be combined with accurate measurements of systemic blood pressure and fluid balance using intra-arterial and central venous pressure lines, respectively.

Methodology.

ICP monitoring requires the placement of a pressure-sensing device into the cranial cavity. Initial work on the direct monitoring of ICP after ventricular puncture was carried out by Guillaume and Janny [1951] and Lundberg [1960]. The following three basic patterns of ICP were described by Landberg:

1.1.Plateau or A waves; increases of ICP in the 540 to 650 mm of water range (40 to 50 mm Hg) that are sustained for 2 to 10 minutes, followed by return to a higher baseline than before. They are indicative of a significant drecrease in brain compliance. 1.2.B waves; these are brief elevations of a moderate degree(i.e., 272 to 408 mm of water range [20 to 30 mm Hg] and are related to fluctuations in respiration and are also indicative of decreased compliance. 1.3.C waves; these are small amplitude fluctuations related to intracranial transmission of arterial pulse.

ICP is most reliably monitored by the placement of an intraventricular catheter that is connected to a pressure transducer and a recording device or continuous strip chart. Placement of an intraventricular catheter can be technically difficult when severe brain swelling leads to compressed ventricles or in instances of ventricular displacement. On the other hand, one advantage of the intraventricular catheter is the ability to decrease intracranial volume by withdrawing small amounts of CSF (1 to 2 ml) during periods of significant brain swelling. Compliance can also be studied in patients with the intraventricular cannula by determining the pressure-volume index (PVI), which consist of plotting the ICP logarithmically against volume [Marmarou and Shulman, 1976]. A small amount of saline (0.5 to 1 ml) of saline is instilled into the intraventricular catheter. The PVI is the volume (ml) needed to raise the ICP by a factor of 10 (Figure 60-2). The normal PVI is approximately 25 in adults and around 10 in infants. Adults values are reached around age 14 years. A decrease in compliance leads to a decrease in the PVI. The risk associated with ventricular catheters include hemorrhage and infection. The Overall risk of ventriculitis is 1% to 5% [Rosner and Becker, 1976] and rises when the catheter has been left in place for more than 3 to 4 days. Other ICP monitoring devices include the subarachnoid bolt, the epidural transducer, an the fiberoptic, intraparenchymal catheter-transducer. The ease of insertion and reliability of the intraparenchymal monitor have led to its increasing acceptance. The normal ICP in children between 1 and 7 years of age ranges from 82 to 176 mm of CSF (5 to 15 mm Hg), and the generally acceptable threshold for treatment of raised ICP is over 200 to 240 mm (15 to 18 mm Hg). The cerebral perfusion pressure should also be monitored and kept well over 50 to 55 mm Hg (the normal cerebral perfusion pressure is 70 to 73 mm Hg in infants and 73 to 77 mm Hg in children) [Shapiro et al., 1994]. Raised ICP is seen in 40% to 60% of patients with severe head injury and in 50% of those who die [Nayaran, 1982].

Utility.

ICP monitoring is definitely indicated in all comatose, head-injure patients with a Glasgow Coma Scale score of 8 or less, as numerous studies have demonstrated that it improves the outcome in this group [Narayan et al., 1982]. It may also be beneficial in the management of patients with brain tumors, slitventricule syndrome, craniosynostosis, and Reye's syndrome. It does not, however, improve the outcome in coma related to severe hypoxic-ischemic encephalopathy [e.g., near drowning], acute encephalitis, or hepatic failure [Leursen, 1997].

Monitoring of Intracranial Pressure from the Anterior Fontanel.

The tension over the anterior fontanel can be used as a gauge of ICP in newborns and infants. A helpful review is provided by Volpe [1995]. The basis for all the available devices is the applanation principle [Salmon et al., 1975], which states that when the anterior fontanel is maintained in the flat position. Pressure on either side is equal. The hand-held devices is pressed over the anterior fontanel and the pressure required to eliminate bulging of the skin is determined; this corresponds t the ICP. The manner of placement of each device over the fontanel is a key issue. In trained individuals, there is excellent correlation between pressure readings obtained after lumbar puncture and those from the fontanellmeters. Usin this device, Volpe et al., [1995] found the ICP in newborns free of intracranial pathology to be 40 to 50 mm of water (2.9 to 3.6 mm Hg). Serial measurements by this noninvasive technique may be helpful in the management of neonatal intraventricular hemorrhage, posthemorrhagic hydrocephalus, bacterial meningitis, and hypoxic-ischemic encephalopathy.

Measurement of Blood-Flow Velocities by Doppler.

Doppler assessment of cerebral blood flow velocity can be obtained serially at the bedside in critically ill neonates. A transducer placed over the anterior fontanel emits high-frequency sound waves that are directed at the pericallosal branch of the anterior cerebral artery. After closure of the anterior fontanel vessels in the circle of Willis can be insonated through the temporal bone. The frequency shifts of the back-scattered echoes are converted into visual images. Blood-flow velocity measurements thus obtained provide indirect information about blood flow because velocity is inversely proportional to the diameter of blood vessel, and cerebral edema might lead to compression of blood vessels. The resistive index is most commonly assessed. It is as follows:

(Peak systolic amplitude of flow Peak diastolic amplitude of flow)/Peak systolic amplitude of flow

It is a useful index of blood flow velocity. Although isolated values are of not much significance, serial

increases in resistive index recordings are indicative of increasing ICP.

CLINICAL MANIFESTATIONS OF RAISED INTRACRANIAL PRESSURE.

Headache.

Supratentorial mass lesions frequently lead to traction on the dura, which is innervated by the trigeminal nerve, thus causing pain that is referred to the frontal and temporal regions, whereas infratentorial structures might lead to pain localized over the occipital regions. The headache is frequently exacerbated by measures that increase ICP (e.g., coughing, bending, sneezing). It might also be worsened by the recumbent position, and patients frequently have a history of headache on awakening in the morning. The duration of the headache is generally brief, lasting days to weeks. Sutures can split in children less than 10 years of age, thus providing temporary relief from symptoms, only to have the headache return within a few days because of progressively increasing ICP. Analgesiscs provide little to no relief. Patients with third ventricular tumors many sometimes find relief by assuming an unusual kneeling position an flexing their necks forward.

Diplopia.

The sixth cranial nerve has the longest intracranial course of all the cranial nerves, thus making it susceptible to displacement and traction from enlarging supratentorial or infratentorial mass lesions. Stretching of cranial nerve VI can lead to its unilateral or bilateral paresis, thus causing a false localizing sign because there is no intrinsic pontine lesion. The patient presents with binocular diplopa, made worse in the direction of gaze of the paretic muscle. There is no relationship of the paresis with the level of ICP.

Decreased Sensorium.

Stupor begins to appear in adults when the ICP reaches the 204 to 540 mm of water (15 to 40 mm Hg) range [Ropper, 1984]. Comparable data are not available for children. The mechanisms postulated include one swollen hemisphere compressing the contralateral hemisphere and creating bihemisphere coma and compression of the ascending reticular formation in the mesencephalic- diencephalic regions.

Impaired Up-gaze.

Pressure over the pretectal region from supratentorial mass lesions impairs upward gaze. The associated midbrain dysfunction leads to mild retraction of the upper eye lids because of sympathetic overactivity. These two elements combine to produce the sunset sign, which is especially obvious in infants in the from of prominent eyes with downward deviation of gaze.

Change in Personality.

Nonspecific manifestations such as irritability, mood swings, apthy, and lethargy are common in infants and children with subacute, progressive increases in ICP.

Excessive Cranial Enlargement.

Increasing intracranial volume from subacute or chronic mass lesions in infants and toddlers frequently leads to splitting of the cranial sutures and macrocephaly. Serial measurements of the head circumference plotted on a head growth chart might demonstrate an upward shift to higher percentiles. Additionally, one might the able to palpate splitting of the sutures; the anterior fontanel may be tense and bulging. Closure of the anterior fontanel, which generally occurs between 8 to 18 months, might also be delayed.

Papilledema.

Papilledema is the most reliable sign of increased ICP; it occurs from edema in the nerve fiber layer of the retina because of impaired retinal venous return as a result of the increased ICP. It may be unilateral or bilateral with supratentorial mass lesions but is bilateral with infratentorial lesions. Most patients do

not complain of visual symptoms, but in the late stages of papilledema, there might be transient visual obscurations, which are fleeting episodes of vision loss lasting seconds. Early papilledema is characterized by a loss of retinal venous pulsations (however, about 20% of normal children also do not demonstrated venous pulsations). This is followed by elevation and blurring of the optic disc margins, tortuosity of the retinal veins, hemorrhages, and exudates (Figure 60-3). In contrast to papillitis, visual acuity remains normal until a late stage. Although the presence of papilledema reliably indicates increased ICP, its absence does not exclude it. In a population of 120 children with craniosynostosis (premature closure of sutures), the presence of papilledema was 98% specific as an indicator for raised ICP, but its sensitivity was age-dependent [Tuite et al., 1996]. It was a reliable indicator of raised ICP in children above the age of 5 years, but not in preschool-age children. It is generally also not seen in infants because of compensation by splitting of the sutures and cranial enlargement. A false impression of papilledema can be created by drusen, alternatively termed colloid or hyaline bodies. They are located over the optic nerve head, dominantly inherited [Fenichel, 1993], more common in Caucasians, and generally seen after the age of 11 years [Glaser, 1978].

Cushing Response.

Compression of the brainstem may lead to slowing of the respiratory rate, bradycardia, and elevation of the blood pressure. These changes are observed only inconsistently, in about one fifth to one third of patients with documented ICP elevations [Marshall, 1979]. In fact, tachycardia is associated with raised ICP as often as in bradycardia.

Acute Pulmonary Edema.

Acute pulmonary edema is a rare but significant complication of cerebral edema [Ducker et al., 1969]. It is triggered by an excessive autonomic discharge leading to increased pulmonary vascular permeability; it is reversible on reduction of ICP.

Brain Herniation Syndromes.

Severe cerebral edema (Figure 60-4) ultimately leads to brain herniation, during which portions of the swollen brain become impacted in abnormal locations (e.g., the tentorial notch or the foramen magnum) [Plum and Posner, 1980]. The displaced brain tissue impinges on vessels, leading to impairment of venous return, additional swelling, and ischemic injury. The following vicious cycle develops, which, if untreated, can be fatal:

Cerebral edema -----> Vascular occlusion ---->Brain ischemia ---> Cellular injury

Transtentorial Herniation. Transtentorial herniation is characterized by the swollen, uncal portion of the temporal lobe becoming displaced in a medial and caudal direction and becoming impacted in the tentorial notch, thus compressing the ipsilateral third cranial nerve, midbrain, ipsilateral cerebral peduncle, and posterior cerebral artery. The initial clinical manifestations include an ipsilateral dilated pupil (resulting from extrinsic compression of the pupillo-constrictor fibers in the outer core of the third nerve); progressive decline in consciousness, loss of oculocephalic (doll's eye) reflexes, the appearance of abnormal postures (decortication), and contralateral hemiparesis. At times there can also be pressure on the contralateral cerebral peduncle, leading, to hemiparesis that is ipsilateral to the mass lesion.

Central Herniation. Central herniation is seen when both diffusely swollen cerebral hemispheres compress the diencephalic structures and midbrain from above. In its early stages, it is characterized by a progressive decline in the level of consciousness, constricted pupils (resulting from diencephalic sympathetic dysfunction), and Cheyne-Stokes respiration. With further progression, there is loss of oculocephalic reflexes, central neurogenic hypervention, and decerebrate posturing that ultimately progresses to a flaccid stated.

Tonsillar Herniation. The cerebellar tonsils become impacted in the foramen magnum, thus compressing the medulla oblongata and the upper cervical spinal cord. This type of herniation can occur with either supratentorial or infratentorial mass lesions, although it is encountered more often with posterior fossa mass lesions. It is characterized by an abrupt loss of consciousness, opisthotonic posturing, stiff neck, irregular respiration, and apnea. The late stages of uncal, central, or tonsillar herniaton are indistinguishable, with presence of flaccid limbs, unresponsive midsize pupils, loss of caloric and oculocephalic reflexes, and irreversible apnea leading to death.

Cingulate Herniation. Cingulate herniation is characterized by shifting of the swollen cingulate gyrus underneath the free edge of the falx cerebri, causing compressing of the ipsilateral or bilateral anterior cerebral arteries and the internal cerebral vein. This leads to infarction of the paracentral lobules.

LUMBAR PUNCTURE IN PATIENTS WITH RAISED INTRACRANIAL PRESSURE.

Lumbar puncture is contraindicated in patients with raised ICP because of the risk of precipitating brain herniation. The ocular fundi should therefore be assessed for papilledema in every patient before initiating the lumbar puncture. If the fundi cannot be visualized and symptoms are suggestive of increased ICP, pertinent diagnostic information may be obtained by CT or MRI scanning. When acute encephalitis and bacterial meningitis are suspected, , administration of antibiotics and scanning can be performed before lumbar puncture. In this case the least amount of CSF necessary for diagnosis is withdraw. If the CSF opening pressure unexpectedly exceeds 200 mm of water, the stopcock of the manometer should be closed, the lumbar puncture needle withdrawn, and diagnostic studies carried out only on the fluid contained within the manometer. A post-lumbar puncture prophylactic dose of mannitol o.25 to 1 gm/Kg, should also be immediately administered in this situation.

MANAGEMENT OF AGUTELY ELEVATED INTRACRANIAL PRESSURE.

Whenever possible, treatment should be directed toward the underlying cause of the raised ICP (e.g., acute encephalitis) and abscess. Other measures, however, are also indicated.

Respiratory Management.

Hyperventilation after endotracheal intubation with maintenance of Paco2 between 25 and 30 Torr effectively reduces ICP by causing cerebral vasoconstriction, thus decreasing intracranial volume. If the patient needs to be intubated a topical anesthetic spray should be used over the vocal cords to minimize stimulation of the brainstem by procedural trauma, which nay raise ICP. In such instances, it is also advisable to lower the ICP by infusing mannitol before the intubation. The drop in ICP occurs within 1 to 5 minutes of initiation of hyperventilation [Ropper, 1984]. ICP can be satisfactorily controlled in two thirds of patients using a combination of a hyperosmolar agent and hyperventilation. Failure to reduce ICP with hyperventilation is a grave prognostic sign. Discontinuation of hyperventilation should be carried out gradually over 24 to 48 hours, since abrupt cessation can lead to a rebound increase in ICP. Elevations in ICP from indirect transmission of elevated intrathoracic pressure to the intracranial vessels can be avoided by sedation and decreasing the inspiratory phase of the respirator [Ersson et al., 1990]. Positive-end expiratory pressure (PEEP) could also theoretically raised the ICP, but this does not appear to be an issue in clinical practice [Shapiro et al., 1994; Frost et al., 1977].

Positioning of the Neck.

Elevation of the head from 15 to 30 degrees facilities venous return from the head, thus helping reduce ICP. This degree of head elevation does not lower the cerebral perfusion pressure [Rosner and Coley, 1986]. Hyperextension, twisting of the neck, and traction on the endotracheal tube should be avoided. The head should not be elevated in hypotensive patients.

Fluid Management.

A central venous pressure line should be placed in patients with significantly increased ICP to help manage fluid balance. Hypotonic intravenous fluids should be avoided because they can precipitate a fluid shift into the brain compartment and exacerbate cerebral edema. A 5% dextrose solution with half normal saline, normal saline, or Ringer's lactate is preferred. The patient should be monitored closely for the syndrome of inappropriate secretion of antidiuretic hormone(SIADH), with measurements of serum and urine osmolality. Fluid intake should be kept at maintenance levels but lowered if the syndrome of inappropriate secretion of antidiuretic hormone begins to appear. Hypovolemia should be avoided.

Hyperosmolar Agents.

Mannitol, urea and glycerol are the most commonly used osmotic agents. They lead to an abrupt increase in intravascular osmolality relative to the brain compartment. This osmotic gradient facilitates a fluid shift from the brain into the vascular space . Mannitol is the most commonly used of these three agents because its intravascular and brain concentrations do not equilibrate as rapidly as they do for glycerol and urea. It is available as a 20% solution. The doses is 0.25 to 1gm/kg given over 5 to 10 minutes as a bolus. Onset mannitol action occurs within 1 to 5 minutes and the duration of action is 2 to 3 hours. Furosemide has a synergistic effect with mannitol in terms of reducing the ICP by virtue of decreasing free water. It might also lower the rate of formation of CSF, but this effect is not significant in the clinical setting.Glycerol is available as a 10% solution, given intravenously in a dose of 1 mg/kg, three to four times a day. Its onset of action is within 30 minutes. The adminsitration of repeated doses of any osmotic agent over a short period of time ( e. g four to five doses over 24 hours) may lead to a rebound increase in ICP (Node and Nakazawa, 1990). Other complications from use of osmotic agents incluide dehydration and electrolyte imbalance (especially hypernatremia). The serum osmolality should be always be maintiained below 320 mOsM/kg. Placement of a central venous line to assess

fluid balance is vital in any subject receiving repeated infusions of osmotic agents.

Corticosteroids

Lipid hydrolysis and free radical-induced lipid peroxidation are inhibited by costicosteroids. (hall et al 1982). this may limit the development of vasogenic edema, but the exact mechanism of action has not been fully established. Although the efficacy of steroidsin the treatment of brain edema associateed with neoplasms is unquestionable, there is no clear proof that they alleviate edema seen with posttraumatic, metabolic, and inflamatory disorders. The recommended dose of dexamethasone in infants and young children is 0.4 to 1 mg/kg/day in four divided doses; the dose in adolescents is 4 mg every 6 hours. Onset of action may take 12 to 24 hours.

Intracranial pressure monitoring device.

Bedside neurologic examinaton is of limited value in a patient who is comatose and has required more than two to there doses of an osmotic agent for control of the clinical manifestations of suspected increased ICP. Placement of an ICP monitoring device in these patients should be considered.

Barbiturates

Petonbarbital is more effective than phenobarbital in acutely reducing cerebral metabolism, which leads to a reduction in cerebral blood flow and intracranial volume, and, thus indirectly, the ICP. Barbiturates are generally used only when standard therapy consisting of osmotic agents, hyperventilation, and head positioning has failed to control the ICP. An initial bolus of 5 to 10 mg/kg of pentobarbital given over 30 minutes is followed by its infusion at a rate of 1 to 5 mg/kg/hour to maintain the serum pentobarbital level between 35 t0 45 ug/ml. The electroencephalogram should also be monitored continously to ensure that the lowering of cerebral metabolism leads to a suppressionburst pattern. Barbiturates should be used only in the intensive care setting, with close monitoring of the mean arterial pressure, ICP, cardiac index, and pulmonary artery wedge pressures. Hypotension, mostly from cardiac depression, develops in 50% of subjects despite adequate volume replacement and may require correction with dopamine or dobutamine. Other complications of barbiturate coma innclude pneumonia and hyponatremia. Althoug barbiturates are effective in lowering the ICP in patients refractory to standard therapy( Heisenberg et al 1988) they do not improve the outcome in

severe head injury(ward et al 1985) metabolic disorders (brain resuscitation clinical trial study group, 1987), or stroke (ropper, 1984).

Relief of Acute Hydrocephalus.

An emergency ventriculostomy can provide temporary relief for the elevated ICP in patients with acute hydrocephalus. This procedure is especially useful in patients with brain tumors because hydrocephalus in some of these patients might be transient, and placement of a permanent ventriculoperitoneal shunt may be avoided. The pressure is monitored continuously and, if it exceeds a certain threshold, CSF is drained. In other instances, however, based on etiology, the neurosurgeon might well consider placement of a permanent ventriculoperitoneal shunt.

PSEUDOTUMOR CEREBRI (BENIGN INTRACRANIAL HYPERTENSION).

Pseudotumor cerebri can occur at any age in childhood. It is termed benign primarily because it does not cause coma or brain herniation. Untreated patients may, however, develop progressive visual loss from ischemic optic neurophaty. Pseudotumor cerebri presents subacutely with daily headache that is made worse by maneuvers that increase ICP (e.g., coughing and bending). Infants may manifest irritability, the sunset sing, and a bulging anterior fontanel. Cranial never VI paresis from the elevated ICP can lead to diplopia that worsens on attempts at lateral gaze [Bergman, 1994]. Other manifestations include tinnitus, blurring of vision, vertigo, decreased visual acuity, and transient visual obscurations. Patients remain alert and fully oriented. Adolescent subjects may be obese; obesity is slightly more common in females than males at this age, but there is no particular gender predilection in infancy or early childhood. The retinal examination discloses papilledema. Bedside and formal visual-field testing may demonstrate enlargement of the size of the blind spot in the advanced stages. Risk factors for the development of pseudotumor cerebri are listed in Box 60-2. No specific etiology is found in some cases. Although the pathophysiology has not been firmly established, elevated venous sinus pressure, with or without sinus thrombosis, is seen consistently in almost all, subjects [Karahalios et al., 1996]. in turn, this leads to decreased egress of CSF into the venous system at the level of the CSF-blood barrier that is located in the arachnoid granulations [Janny et al., 1981], thus raising ICP. MRI and CT scan studies are usually normal. Infrequently, however, the ventricles might be compressed and slitlike or there might be evidence of venous sinus thrombosis. Lumbar puncture is needed for establishing a definitive diagnosis; the opening pressure is elevated (over 200 mm) and the

CSF is clear, with normal cell count, protein, and glucose content. The treatment consists of a series of measures that vary according to whether or not visual function has been compromised. In patients presenting with headache but with no compromise of visual function the first therapeutic step is eliminating the underlying precipitant (if possible), like vitamin A or tetracycline. The management of pseudotumor cerebri at this stage can be affected by the use of agents that decrease the formation of CSF (i.e., acetazolamide [20 mg/kg/day in two divided doses] or furosemide [1 mg/kg/day in two divided doses]). Patients receiving acetazolamide should be monitored for side effects like drowsiness; anorexia; numbness of the hands, feet, or face; and renal calculi, whereas those taking furosemide should be monitored for hypokamemia. There are no data on the comparative efficacy of furosemide versus acetazolamide. Weight reduction measures are also recommended in all obese subjects. A 2- to 3-week course of dexamethasone may also be benefical [ Fenichel, 1993], but there is a risk that the weight gain from the steroid use, and the discontinuation of steroids, may exacerbate the pseudotumor. Serial lumbar pictures, done every 5 to 7 days, with drainage of 15 to 20 ml of CSF on each tap to bring down the closing pressure below 200mm is sometimes useful. Pain at the lumbar puncture site and post-lumbar puncture headache are potential complications. Simple analgesics like acetaminophen and ibuprofen combined with bed rest are used to treat these complications. A careful neuro-ophthalmologic examination consisting of measurement of the visual acuity and visual fields should be performed every 1 to 3 months. Patients who demostrate compromise of visual function in spite of medication should undergo optic nerve sheath fenestration, a surgical procedure that reduces pressure on the nerve. Medical therapy should continue. In a study of 29 eyes of patients with pseudotumor cerebri that were subjected to optic nerve sheath fenestration and followed for a mean of 15.7 months [Goh et al., 1997], the visual acuity improved in four eyes (13.7%), stabilized in 22 eyes (76%), and deteriorated in 3 eyes (10.3%). A lumboperitoneal shunt [Johnston et al., 1988] may also be used when pseudotumor cerebri is recalcitrant to standard medical therapy.

CEREBRAL EDEMA IN DIABETIC KETOACIDOSIS

Mild degrees of cerebral edema, characterized by obliteration of the cortical sulci and minimal compression of the lateral ventricles visualized on CT scans, are a common occurrence in the course of treatment of juvenile diabetic ketoacidosis [Krane et al., 1985]. However, most of these patients remain clinically asymptomatic. Severe cerebral edema, on the other hand, is a rare but potentially lethal complication with a mortality rate of 90% [Krane et al., 1985]. Paradoxically, it becomes apparent 6 to 10 hours after initiation of therapy with intravenous fluids and insulin, at a time when the blood glucose levels are falling and adequate circulation has been restored [Krane et al ., 1985]. The pathogenesis is not clearly understood, but it may be due to osmotic dysequilibrium between the blood and the brain compartments. Diabetic ketoacidosis is associated with accumulation in the brain of polyols (sorbitol, xylitol, and dulcitol) and other unidentified, osmotically active substrates termed

idiogenic osmoles. An osmotic dysequilibrium between state may develop because the intravascular hyperosmolality, resulting in a large fluid shift into the brain [Prockop, 1971; Arieff and Kleeman, 1973]. Hale et al [1997] believe that this is more likely to occur in patients with low initial serum sodium levels and effective serum osmolalities. Other investigators have felt that the syndrome is related primarily to a rapid reduction in serum glucose and osmolality and is not caused by movement of sodium into the brain. Acidosis does not play any significant role in the pathogenesis. The resultant brain swelling leads to an abrupt deterioration in the level of consciousness in a patient who was previously becoming more alert. Central or uncal herniation may develop, leading to changes in pupillary size, tonic posturing, loss of oculocephalic reflexes, and respiratory arrest. The management calls for immediate intravenous administration of mannitol (0.25 to 1 gm/kg), followed by endotracheal intubation and hyperventilation if necessary.

EXTERNAL HYDROCEPHALUS

External hydrocephalus is a common cause of excessive cranial enlargement in infancy. The term is somewhat ambiguous because the exact site and mechanism of fluid accumulation is in question [Hamza et al., 1987]. Although usually benign, the possibility of active communicating hydrocephalus must always be considered. More common in males, it might also be responsible for some proportion of cases of familial macrocrania. The patients generally develop an occipitofrontal circumference that overshoots the 95th percentile and then follows its curve. There be mild frontal bossing. The anterior fontanel is enlarged in size but is not tense or bulging. The developmental milestones and neurologic examination are within normal limits. The long-term outcome is also normal [Nishimura et al., 1996]. External hydrocephalus is most likely caused by a transient defect in the absorption of CSF at the level of the arachnoid villi. The head CT scan demonstrates mild enlargement of the frontal horns of the lateral ventricles, prominent cortical sulci and sylvian fissures, increase in the size of the ambient cisterns, and enlarged extra-axial, CSF-containing spaces in the frontal and interhemispheric regions. The disorder needs to be differentiated primarily from benign subdural effusions of infancy. Both lesions appear similar on CT scans, but MRI helps distinguish the twobenign subdurals may be characterized by hyperintensity on T1-weighted, proton-density, or T2-weighted images. Flow voids from vessels traversing subarachnoid space can be seen on a least one of these imaging sequences in patients with external hydrocephalus but not in those with benign subdurals [Aoki, 1994].

CRANIOSYNOSTOSIS Secondary craniosynostosis is related to micrencephaly, with premature suture closure occurring because of a lack of brain growth, It does not lead to increased ICP. Primary, premature closure of the cranial sutures can, however, lead to elevated ICP. It occurs with an incidence of 0.4 per 1000. Most cases are sporadic, although both autosomal-recessive and autosomal-dominant forms also occur. At

least 50 syndromic conditions have been documented in association with craniosynostosis [Sharpiro, 1994]. Sagittal synostosis the most common lesion (leading to scaphocephaly) followed by coronal synostosis (leading to brachycephaly or plagiocephaly). Premature closure of one suture leads mainly to a cosmetic deformity. Increased ICP is more likely to be encountered with premature closure of multiple sutures. It generally manifests in the form of irritability, opisthotonic posturing, headache, vomiting, and papilledema. Using epidural monitors, Reiner et al. [1982] reported a 33% a incidence of increased ICP in patients with craniosynostosis. There are probably multiple mechanisms underlying the premature closure of the sutures, including genetic factors, teratogens, metabolic bone decrease, intrauterine positioning, and moulding [Sharpiro, 1984]. Intracranial abnormalities like septo-optic dysplasia and ventriculomegaly can coexist. Crouzon's disease is an autosomal-dominant disorder because of mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. It is characterized by early closure of any or all sutures in association with midface hypoplasia [Theone, 1995]. Patients manifest hypertelorism, exophthalmos, a parrotbeaked nose, hypoplastic maxilla, and prognathism. Progressive visual and hearing loss occur in half the subjects, and mental retardation in a third. Apert syndrome is characterized by coronal synostosis and syndactyly, hypertelrism, exophthalmos, normal intelligence, cataracts, and a high, pointed palate [Theone, 1995]. Above average parental age has been reported in sporadic cases. Mutations involving the FGFR2 gene have once again also been observed. The kleeblattschadel (cloverleaf) deformity is seen with primary craniosynostosis involving all sutures. It may be inherited as a recessive or dominant trait. Skull radiographs in craniosynostosis patients reveal obliteration of the sutures and sclerosis along their margins and a beaten silver appearance. CT scans are helpful in excluding associated intraparenchymal lesions. Elevated ICP can be established by lumbar puncture or epidural ICP monitors. Surgical treatment, whether for cosmetic reasons alone or for alleviation of increased ICP, requires a team approach, using the expertise of a primary care physician, neurosurgeon, facial plastic surgeon, neuro-ophthalmologist, anesthesiologist, and social worker. The operative procedure may vary from strip craniectomy along the suture margins to more extensive plastic procedures. There is a high incidence of recurrence of increased ICP in patients with syndromic craniosynostosis. In a study of 22 consecutive infants with syndromic craniosynostosis who underwent initial surgery between 6 to 18 months, Pollack et al. [1996] found that eight to 22 (36%) developed asymptomatic increases in ICP at a median of 16.5 months after the initial surgery.