Neurological Emergencies - part 2 pptx

Alternatively, brain injury may lead to cerebrovascularcongestion and an excess cerebral blood volume, resulting incerebral hyperaemia, that is, an absolute or relative increase in the c

disruption of autoregulation of blood flow Penetratinginjury may be clinically silent, or produce focal neurologicaldeficit, due either to the haematoma or to the underlyingneuronal injury Focal contusions occur both ipsilateral andcontralateral to a fracture, as for example bifrontal contusionscomplicating an occipital fracture As with subduralhaematoma, delayed deterioration may occur in a patient with

a brain contusion or intraparenchymal haematoma days afterthe injury

Figure 2.1 (b) Patients with an acute subdural haematoma are seen after high speed road traffic accidents, falls, or assaults They are commonly associated with other parenchymal injuries, which may affect outcome as much as the haematoma itself.

The haematoma often occurs over the temporal pole either from tearing of bridging veins, or from laceration of the brain and disruption

of sur face ar teries The common combination of temporal lobe

laceration and contusion with an associated subdural haematoma is known as “burst temporal lobe”

Brain swelling and raised intracranial pressure

Intracranial pressure increases as a consequence of a rapidlydeveloping intracranial mass lesion, hypoxia, hypercarbia,during an epileptic seizure, and in acute hydrocephalus Brainoedema is defined as an increase in brain volume due toincrease in brain water content Klatzo defined it as

“vasogenic”8 because of disruption of the blood–brain barrierand escape of water and plasma into the extracellularcompartment, in contrast to “cytotoxic oedema” in which anoxious factor produces intracellular swelling withoutincreased vascular permeability.9,10 The oedema around a

Figure 2.1 (c) Intraparenchymal haematomas occur from disruption of vascular elements.

This may be focal from a penetrating injur y, or diffuse from rotational acceleration, producing widespread haemorrhage and axonal disruption Penetrating injur y may be clinically silent, or produce focal neurological deficit, due either to the haematoma or the underlying neuronal injur y Focal contusions occur both ipsilateral and contralateral to a fracture, for example, bifrontal contusions complicating an occipital fracture

contusion or haematoma was initially thought to be vasogenic;protein rich fluid leaking into the extracellular space,increasing the water and sodium in the brain to produce “masseffect” Marmarou, however, has shown that most of the water

in areas of brain contusion is in fact intracellular andrepresents “cellular” oedema, caused by ischaemia.11 This inturn produces astrocytic swelling and increased release ofexcitatory amino acids and a consequent failure of membraneion pumps and cellular ionic homoeostasis This is recognisableradiographically as an increase in the signal on T2 weightedMRI and as radiolucent areas on CT

Alternatively, brain injury may lead to cerebrovascularcongestion and an excess cerebral blood volume, resulting incerebral hyperaemia, that is, an absolute or relative increase

in the cerebral blood flow in relation to cerebral metabolicdemand

The consequence of raised intracranial pressure is thedevelopment of pressure gradients across the midline,between supratentorial and infratentorial compartments, andbetween the cranial and spinal compartments across theforamen magnum In 1965 Langfitt showed how raisedsupratentorial pressure produces a rise in infratentorialpressure which subsequently plateaus and falls as the cisternaambiens becomes blocked by tentorial herniation The brain isshifted away from the region of higher pressure, so midlinestructures are pushed laterally, causing the cingulate gyrus toherniate under the fixed free edge of the falx This distorts thepericallosal arteries, and may occlude the foramen of Munro.The cerebrospinal fluid (CSF) drainage of the contralateralventricle is obstructed, so the ventricle dilates; the ipsilateralventricle may become compressed, giving characteristicfeatures suggesting raised intracranial pressure (ICP) on cross-sectional imaging Further increases in ICP produce tentorialherniation, with a temporal or parietal lesion compression ofthe ipsilateral oculomotor nerve and midbrain Furtherdistortion leads to posterior cerebral artery compression.Bilateral or frontal lesions produce posterior herniation,compressing the tectal plate, resulting in failure of upwardgaze and bilateral pupillary abnormalities Infratentorialmasses or further herniation of a supratentorial mass results inherniation through the foramen magnum As the medulla and

cerebellar tonsils are pushed inferiorly, distortion of thevasomotor and respiratory centres leads to circulatory collapseand respiratory arrest.

Pathophysiology

Mechanisms of primary brain injury after trauma

The primary injury, which can be correlated with prolongedcoma and impaired motor response, was recognised by Strich

in 1961 as a diffuse degeneration of the subcortical matter,subsequently termed diffuse axonal injury (DAI).Experimental work with primates confirms this to be aconsequence of inertial loading of the head, with prolongedcoronal angular acceleration Microscopic pathologicalfindings consist of small haemorrhages in the corpuscallosum, septum pellucidum, deep grey matter of the cerebralhemisphere, and dorsilateral quadrant of midbrain and pons.Disrupted and swollen axons with globular ends known as

“retraction balls of Cajal” are observed at an early stage After

a few weeks clusters of neuroglia form around the severedaxons and wallerian degeneration of fibre tracts occurs.12

Clinically, diffuse axonal injury is thought to be responsiblefor a broad spectrum of injury from mild concussion in which

no structural lesion can be demonstrated and completeclinical recovery ensues, to prolonged coma and death ininstances of much greater angular acceleration

The events leading to axonal disruption have recently beenexamined Povlishock and others have shown that this is aprocess requiring several hours to complete and may bereversible before frank axonal disruption occurs, at least insome axons.13

It should of course be stressed that not all primary injury isdiffuse Focal contusions and lacerations are seen, especiallyafter falls and blows to the head, often involving the inferior(orbital) surface of the frontal lobes and the anterior poles

of the temporal lobes Brain oedema around contusions maylead to late clinical deterioration as a result of mass effect andbrain shift

Mechanisms of secondary brain injury after trauma

Secondary brain injury follows after primary damage, either

as a consequence of the TBI itself, or due to systemic injury or

“insult” TBI can be responsible for the development of anintracranial haematoma, brain swelling, raised intracranialpressure, and ischaemia, all of which may be worsened bysystemic hypoxia, hypotension, or pyrexia

Ischaemia

Since Douglas Miller14,15 and others showed the strongrelationship between deranged physiology, which wouldlikely reduce brain oxygen delivery, and outcome, and theautopsy evidence of near universal, widespread, ischaemicbrain damage after fatal head injury, investigators have sought

to determine the causal pathophysiological mechanismsinvolved

Cerebral perfusion pressure

Cerebral blood flow has been found to change passively withcerebral perfusion pressures (CPP) after head injuries of differingseverity, suggesting that autoregulation is impaired However,the cerebrovascular response to changes in arterial PaCO2is oftenpreserved One explanation of pressure passive changes is thatthe autoregulatory curve has been shifted to the right, so thatthe minimum acceptable CPP needs to be higher than normal

to ensure cerebral blood flow Jugular venous oxygen saturationdata and transcranial Doppler middle cerebral artery flowvelocity studies suggest this threshold is a CPP of 70 mmHg,whether due to raised ICP or reduced arterial pressure A shift ofthe autoregulatory curve due to a generalised increase incerebral vascular resistance after TBI may be due to artificialventilation or spontaneous hyperventilation Alternatively, theabsence or overproduction of luminal and abluminalmodulators, such as endothelin and nitric oxide, maycontribute to an autoregulatory threshold shift.16,17

Arterial hypotension

Arterial hypotension can occur immediately after traumadue to other injuries such as haemorrhage, cardiac

tamponade, haemopneumothorax, myocardial or spinal cordinjury Experimental models of diffuse brain injury such as theimpact acceleration model18 produce transient hypotensionfor minutes after severe injury Intrinsic myocardial disease,inadequate fluid replacement after osmotic diuretics,aggressive hyperventilation, and anaesthetic drugs (such asbarbiturates and proprofol) can all contribute Sepsis mayfurther conspire to lower the blood pressure

Pyrexia

Pyrexia is defined as a body temperature of greater than37°C and is common following TBI There has been muchrecent interest in the incidence, associations, pathogenesis,affect on outcome, and management The incidence ofpyrexia of greater than 38°C in the first 72 hours following TBIhas been reported to be as high as 68% in closed head injury.19

Fever most commonly occurs in patients with closed headinjury and intracranial haemorrhage, with the risk increasingwith prolonged hospital stay (93% of patients staying longerthan 14 days).20

In many patients it is difficult to determine whether anincrease in temperature is a consequence of their brain injury,coexisting conditions, or their treatment Evidence forinfection was found in 74% of the febrile patients and 50% ofthe afebrile patients This makes it difficult to determinewhether there is a causative relationship between hyperthermiaand poor outcome, or purely an association.21Indeed, previouslypublished TBI data showed pyrexia to be prognosticallyimportant, but limitations of the modelling process failed to

highlight that pyrexia was associated with a favourable

outcome.22,23

Several early studies demonstrated an association betweenfever and a poorer outcome following TBI More recently therehave been attempts to quantify the impact of hyperthermia

on outcome In the paediatric population early hyperthermiawas found to be an independent predictor of poor outcome(OR 4·7) and prolonged ICU admission

Pilot studies supported the view that hypothermia would

be beneficial.24 However, a well constructed randomisedcontrolled trial has recently disproved this promising

intervention Patients in the hypothermia group showed nobenefit in functional recovery25 and required moreinterventions to support their systemic circulation Treatmentwith hypothermia, with the body temperature reaching 33°Cwithin eight hours after injury, is not effective in improvingoutcomes in patients with severe brain injury.26–28

Hypoxia

Finally, pulmonary disorders (atelectasis, contusion,infection, or acute respiratory distress syndrome) and areduced haemoglobin oxygen carrying capacity (anaemia)may compromise tissue oxygen delivery Reduced oxygendelivery to regions where cerebral blood flow is alreadycompromised may of course worsen ischaemia

Recently, researchers have combined microdialysis, whichcontinuously monitors the chemistry of a small focal volume

of the cerebral extracellular space, and positron emissiontomography (PET), which conversely establishes metabolism ofthe whole brain for the duration of the scan Both techniqueswere applied to head-injured patients simultaneously to assessthe relationship between microdialysis (measures of oxygendependent metabolism and glutamate) and PET (oxygendelivery and consumption) parameters Hyperventilationresulted in a significant increase in oxygen extraction, inassociation with a reduction in glucose, but no significantchange in glutamate.29The same researchers have reported anestimated ischaemic brain volume of up to 20% of the brainvolume (DK Menon, personal communication) Therefore it issurprising that none of the microdialysis probes were able todetect changes associated with ischaemia One reason might bethat the pathology is not a simple failure of oxygen delivery,but rather a failure of oxygen utilisation.30,31

After traumatic brain injury it is hypothesised that there are

a number of secondary biochemical processes that result inworsening of neurological damage Excitotoxicity, freeradicals, pro-inflammatory cytokines, and ecosanoids have allbeen shown in animal models, and some in human studies, to

be involved in the processes that occur after traumatic injury

to the brain

The excitatory amino acids aspartate and glutamate arereleased in a threshold manner in response to a reduction incerebral blood flow (CBF < 20 ml 100 g−1/min−1) and produce

rapid cell death (3–5 minutes) via activation of the N-methyl

D-aspartate (NMDA) receptor and associated Ca2+ion channel.Excitotoxicity may be mediated by an increase in induciblenitric oxide synthase (iNOS) in astrocytes and microglia, NOthen forming a “super-radical” after interaction with O2 freeradicals.32

The use of antagonists at the NMDA receptor complex hasbeen the subject of extensive investigation; these have failed toshow a significant improvement (>10%) in the primary endpoint for each study Explanations for such results include: poorstudy design; confounding influence of systemic secondaryinsults; and sensitivity of outcome measures.33 As excitatoryamino acids may have a role in hyperglycolysis after TBI, interest

in this potential mechanism of neuronal injury persists Inflammation

Following acute brain injury there is increased intracranialproduction of cytokines, with activation of inflammatory

cascades McKeating et al have shown a transcranial 11 : 1

cytokine gradient in the sera of TBI patients requiringintensive care after acute brain injury.34,35

Adhesion molecules control the migration of leucocytes intotissue after injury and this process may result in still furthercellular damage After TBI altered serum concentrations ofsoluble intercellular adhesion molecule (sICAM)-1 and solubleL-selectin (sL-selectin) can be correlated with injury severityand neurological outcome.36–38

Despite the strong association demonstrated between thesesoluble adhesion molecule concentrations in serum and severity

of injury and outcome, there have been no successful attempts

to beneficially modify this complex process A phase III trial

is recruiting patients to receive Dexanabinol (HU-211).39 This

is a cannabinoid with a diffuse range of actions, includinganti-inflammatory effects The intracranial pressure data fromthe phase II trial support further investigation of this

compound The treatment group (phase II)40 had significantlyless intracranial pressure problems on the second and thirdpostinjury days, suggesting that the agent may have modifiedoedema formation However, the outcome data wereconfounded by imbalanced randomisation, resulting in morepatients having motor score 2 (extension) in the placebo group.The Glasgow Coma Scale (GCS) is not linear and such patientsare much less likely to improve than patients who have motorscore 3 or better Therefore, the randomisation resulted in biasthat cannot be “balanced” by more GCS 7 patients

Free radicals

Direct biochemical evidence for free radical damage andlipid peroxidation in human injury of the central nervoussystem (CNS) is hampered by methodological difficulties.However, indirect evidence suggests a key role for oxygenradicals CNS injury results in decompartmentalisation of ironfrom ferritin, transferrin, and haemoglobin, and Fe2+catalysesreactions to give free radicals

Eicosanoids

Normal cellular function relies upon transitory activation ofenzymes by Ca2+ If this Ca2+ signal is excessive, dysfunctionalactivation of phospholipases, non-lysomal proteases, proteinkinases and phosphatases, endonucleases, and NO synthasewill ensue The activation of phospholipases releases free fattyacids which, in excess, cause increased mitochondrialmembrane permeability to protons and uncouple oxidativephosphorylation Activation of phospholipase A2 producesexcess arachadonic acid (AA), inducing endothelial dysfunctionand derangement of the blood–brain barrier Moreover, theoxidation of AA by cyclo-oxygenase and lipoxygenase pathwaysresults in excess production of eicosanoids with free radicalproperties and adverse effects upon the microvasculature Theresultant effect is vasoderegulation, worsening ischaemia, andmicrovascular thrombosis

Indirect evidence for the role of failure of calciumhomoeostasis after head injury comes from the prospectiverandomised controlled trials of nimodipine.41 A trend toward

more favourable outcomes was noted in patients withtraumatic subarachnoid haemorrhage.42,43

Hyperglycolysis

Experimental studies of TBI have shown that cerebralhyperglycolysis is a pathophysiological response to ionic andneurochemical cascades induced by injury.44,45This observationhas important implications regarding cellular viability,vulnerability to secondary insults, and the functional capability

of affected regions Post-traumatic hyperglycolysis has also beenshown in humans Hyperglycolysis was documented in six ofthe 28 patients in whom both flucrodeoxyglucose positronemission tomography (FDG-PET) and cerebral metabolic rate foroxygen (CMRO2) determinations were made within 8 days ofinjury Five additional patients were found to have localisedareas of hyperglycolysis adjacent to focal mass lesions.46

These clinical data support the experimental results, butunfortunately do not indicate which specific cell types areresponsible It is possible that the cells exhibitinghyperglycolysis are actually peripheral immune cells whichhave migrated into the brain, the observed metabolic patternbeing typical of polymorphonuclear cells

Hyperglycaemia

There is increasing evidence that hyperglycaemia mayaggravate ischaemic injury of the CNS, including spinal cordinjury Glucose solutions should therefore not be used duringthe acute phase of resuscitation and blood glucose must beclosely monitored (hourly); serum glucose above 11 mmolLshould be treated by insulin infusion.47 Evaluation of thecombined effect of hypotension and hyperglycaemiaoccurring in the first 24 hours after severe head injury showedthat mean arterial pressure (MAP) and blood glucose arelinearly related to mortality Regression analysis shows thateach has an independent effect Moreover, the relationshipbetween blood glucose and mortality is stronger than therelationship between MAP and mortality.48Further studies onthe combined effect of hyperglycaemia and hypotension onmortality after head injury are needed because this studysuggests, but does not prove, an additive, causal association

Apolipoprotein E ε4

This protein, synthesised by reactive astrocytes, is responsiblefor transporting lipids to regenerating neurons, promotingrepair, and construction of new cell membranes and synapses.Experimental data have suggested that apolipoprotein E(apoE) is important in the response of the nervous system totrauma There are three common alleles of the apoE gene, ε2, ε3,and ε4; there is evidence of substantial variation in behaviour ofthese isoforms As is now widely recognised, apoE genotype isthe most important genetic determinant of susceptibility toAlzheimer’s disease, and acts synergistically with a previous

history of TBI A recent study by Teasdale et al demonstrated a

significant genetic association between apoE polymorphism andoutcome, supporting the notion of a genetically determinedinfluence In fact, patients with ε4 are more than twice as likely

to have an unfavourable outcome as those without.49,50

Principles of care

Assessing the patient

The management of individual brain-injured patients, andthe formulation and application of guidelines, depends uponthe use of a widely accepted and applicable method ofassessment and classification of the level of consciousness.The Glasgow Coma Scale, and its derivative the GlasgowComa Score, are widely used for assessing patients before andafter arrival at hospital (Table 2.1) Many studies support theirrepeatability, validity, and clinimetric properties.51

The Glasgow Coma Scale provides a framework fordescribing the state of the patient in terms of three aspects ofresponsiveness: eye opening, best motor response, and verbalresponse, each stratified according to increasing impairment.The distinction between normal and abnormal flexion can bedifficult to make consistently and is rarely useful inmonitoring the individual patient; it is, however, relevant toprognosis and is therefore used to classify severity in groups ofpatients The Glasgow Coma Score can provide a singlesummary figure and a basis for systems of classification butcontains less information than a description separately of thethree responses The three responses of the original scale, not

the total score, should be used in describing, monitoring, andexchanging information about individual patients.

Investigation

Intracranial lesions can be detected radiologically beforethey produce clinical changes Rather than awaitingneurological deterioration, early imaging reduces the delay indetection and treatment of acute traumatic intracranial injuryand is reflected in better outcomes Exclusion or demonstration

of intracranial injury can also guide decisions about theintensity and duration of observation in less severe injuries.There has been a progressive shift away from simple skullradiography as a source of circumstantial evidence ofintracranial damage towards CT scanning to provide definitivedata In the absence of randomised comparisons of differentinvestigative strategies, indications for imaging at presentationafter TBI depend upon the likely yield in different categories ofpatient Although most patients with minor head injury can bedischarged without sequelae after a period of observation, in a

Table 2.1 The Glasgow Coma Scale and Score

small proportion their neurological condition deteriorates andrequires neurosurgical intervention for intracranial haematoma.The objective of the Canadian CT Head Rule Study was todevelop an accurate and reliable decision rule for the use ofcomputed tomography (CT) in patients with minor head injury.Such a decision rule would allow physicians to be more selective

in their use of CT without compromising the care of patientswith minor head injury (Table 2.2).52

Referral

The speed with which patients who would benefit fromneurological and neurosurgical care are identified, referred,and transferred may critically influence their outcome There

is evidence that delays and errors in early management haveoccurred in those with unfavourable outcome even aftertransfer to neurosurgical centres The benefits of specialistneurological care include the availability of skills and facilitiesfor intracranial surgery, expertise for patient assessment, andcapability for sophisticated monitoring and management ofintracranial pathologies that constitute neurological intensivecare (NICU) (Box 2.1) There are also benefits to be accrued inthe access to enhanced knowledge and expertise resultingfrom the concentration of experience

Transfer

It is important to consider the effects of the structure of thetrauma service on the care of patients with severe TBI In theUnited Kingdom, this was addressed in the recent WorkingParty Report from the Royal College of Surgeons of England.Neurosurgical services are structured on a regional basis, withone tertiary referral centre serving many hospitals that admitpatients with traumatic injuries The trauma service isstructured on a district basis; this means that many patientsare managed by clinicians without neurosurgical centres whohave little experience or expertise in this field As a result,management is often discussed by telephone, many patientsare transferred between hospitals with the additional risksinvolved, and some are actually managed outside neurosurgicalcentres for the duration of their hospital stay.53 It must beadmitted, however, that management often varies even

between neurosurgical centres.54,55 The publication ofguidelines will hopefully standardise and improve care.56

Patients with an impaired level of consciousness havephysiological instability that can result in secondary insultsduring transport and a worse outcome These adverse events

Table 2.2 (a) Risk of an operable intracranial haematoma in injured patients

Post-traumatic 1 in 6700 amnesia (PTA)

Skull fracture 1 in 81 Skull fracture and PTA 1 in 29

Skull fracture 1 in 5

Skull fracture 1 in 4

Table 2.2(b) Canadian CT head rule – minor head Injury*

Five high-risk factors:

1 Failure to reach GCS of 15 within 2 hours

2 Suspected open skull fracture

3 Sign of basal skull fracture

4 Vomiting >2 episodes

5 Age >65 years

Two additional medium-risk factors:

1 Amnesia before impact >30 minutes

2 Dangerous mechanism of injur y

The 3121 patients had the following characteristics: mean age 38·7 years; GCS scores of 13 (3·5%), 14 (16·7%), 15 (79·8%); 8% had clinically impor tant brain injur y; and 1% required neurological

inter vention 52

The high-risk factors were 100% sensitive (95% CI 92–100%) for predicting need for neurological inter vention, and would require only 32% of patients to undergo CT The medium-risk factors were 98·4% sensitive (95% CI 96–99%) and 49·6% specific for predicting clinically impor tant brain injur y, and would require only 54% of patients to undergo CT.

* Data from Stiell et al 52

can be minimised by resuscitation before transfer, invasivemonitoring, and care by appropriately trained staff, before,during and after transport.

Intensive care

Historically the role of the neurosurgical intensive care unithas been to prevent secondary brain damage following a TBI.The mainstay of this approach has been to correctmacroscopic, measurable, physiological variables, such asblood pressure, oxygenation, and intracerebral pressure to

“normal” or “supranormal” levels The assumption is thatmanipulation of the physiological response to injury willimprove outcome

It is thought that the final common pathway in all acutebrain injury is failure of oxygen delivery (Do2), that is,ischaemia Specialised monitors have been developed to alertthe clinician to critical reductions in DO2

The fundamental aim of intensive care management is toavoid secondary insults and to optimise cerebral oxygenation

by ensuring a normal arterial oxygen content, and by

Box 2.1 A patient with a traumatic brain injury should bediscussed with neurosurgery

• When a CT scan in a general hospital shows a recent intracranial lesion

• When a patient fulfils the criteria for CT scanning but this cannot

be done within an appropriate period

• Whatever the result of any CT scan, when the patient has clinical features that suggest that specialist neurological assessment, monitoring, or management are appropriate These reasons include:

– Persisting coma (GCS <9, no eye opening) after initial resuscitation

– Confusion persists for more than 4 hours

– Deterioration in conscious level after admission (a sustained decrease in one point in the motor or verbal GCS subscores,

or 2 points on the eye opening subscale of the GCS)

– Persistent focal neurological signs

– A seizure without full recover y

– Compound depressed fracture

– Definite or suspected penetrating injur y

– A CSF leak or other sign of base of skull fracture

maintaining cerebral perfusion pressure (CPP) at a level greaterthan 70 mmHg This figure may be modified depending onjugular bulb oxygen saturation (SjO2) measurement While theactual level of ICP may be less important, in general it should

be maintained at less than 25 mmHg.57–60 Most ICP reducingtherapies are double-edged swords and, it should be noted,have not been subject to large prospective randomised trials.The Cochrane Injuries Group has highlighted the lack ofevidence61,62 for much of the therapies used in TBI63 and arecoordinating the largest ever, randomised controlled trial inhead injury, evaluating the effect of corticosteroids(www.crash.lshtm.ac.uk/Newsletter00No29-Oct01.htm)

Intracranial pressure monitoring

Even though ventricular fluid pressure is still regarded as thegold standard, most centres now use solid-state intraparenchymalmonitors that are usually placed into the right (non-dominant) frontal region through a small burrhole While theICP level is important (normal 10 mmHg, acceptable upperlimit 25 mmHg), more significant is the CPP, calculated as thedifference between mean arterial pressure and intracranialpressure, since CPP is the principal determinant of cerebralblood flow (CBF) The zero reference point for the ICP catheterand the arterial pressure transducer should be the same There

is a small risk of catheter displacement, haematoma, and drift

of the zero baseline, but this has not been found to beclinically significant; if ICP readings are incompatible withother findings, however, it is worth considering removal andreinsertion of another catheter Other methods ofmeasurement include ventricular catheterisation – passing acatheter into the lateral ventricle through the non-dominantfrontal lobe.58,60 There are small risks on insertion of such acatheter, and the risk of ventriculitis increases with time(particularly after 7 days), and with sampling CSF from thecatheter It can easily be checked against zero pressure, and can

be used to withdraw CSF to reduce ICP Future measurement ofICP may include a continuous estimate of intracranialcompliance Tissue perfusion is more likely to be related tocompliance than pressure and critical volumetric compensatoryexhaustion will be detected earlier with this measure, using, forexample, the Spiegelberg device (Figure 2.2)

Cerebral metabolic monitoring

Cerebral metabolic monitoring (CMM) has a long historyand has developed as the technology has permitted Indeed,technology may have been the driving force for some of therecent scientific publications In general terms, CMM can bedivided into global and focal, and within these broadcategories bedside or remote monitors can be used

Before describing a catalogue of the available monitors wemust ask what it is that we wish to detect No monitor willimprove outcome itself, and this is made more likely if wemonitor intermediate physiological variables with little

Figure 2.2 (a,b) Spiegelberg compliance monitoring device.

Future measurement of ICP may include a continuous estimate of intracranial compliance Tissue per fusion is more likely to be related to compliance than pressure, and critical volumetric compensator y

exhaustion will be detected earlier with this measure The Spiegelberg device is such a monitor and is currently available

(a)

(b)

relationship to consumer orientated end-points (quality ofsurvival) There has been a tendency to “make the measurableimportant, rather than making the important measurable”.Ischaemia

Oxygen Secondary ischaemic damage has been shown, timeand again, after TBI Therefore a monitor that provides an earlywarning of impending ischaemia should offer promise However,increasingly we believe that the pathophysiological process thatleads to neuronal death is mitochondria failure This will not bedetected by any monitor of the adequacy of global oxygendelivery (jugular bulb oxygen saturation SjvO2) or regional braintissue oxygen tension (PtiO2).64 There are data to show arelationship between both these variables and outcome in a smallnumber of patients but both lack sensitivity and specificity

Cerebral blood flow Measurements of CBF, regional (PET,

Xe133, MRI-PWI) or global (Kety Schmidt), cannot predict whatlevel of oxygen delivery is required to meet metabolic demandand, sadly, PET lacks the refinement of double labelling andflow and metabolism cannot be simultaneously recorded.There is increasing evidence that metabolic requirements foroxygen are extremely low after TBI and previously recognisedthresholds may not equate with neuronal damage after TBI.Hyperglycolysis may be an example of mitochondria adapting

to failure of oxidative metabolism

Intermediate metabolites Intermediate metabolites ofoxidative metabolism can be assessed by brain microdialysisfluid, chemical shift imaging (CSI–MRS), and sampling of thejugular venous blood Glucose, lactate, pyruvate, their ratio,and byproducts of membrane breakdown (glycerol) haveall been assessed, and phenomenology that supports currentthinking has been reported

There are few randomised trials that have compared therapy

to treat therapeutic goals generated by such monitors

Robertson et al conducted a pilot study in which patients

were block randomised to be treated according to an SjvO2

endpoint or an ICP threshold The result was a trend to morefavourable outcomes and less intractable ICP problems in theICP treatment cohort.65

Cerebral metabolic monitoring: pathobiological processesExcitotoxicity Brain microdialysis has been used to monitorexcitatory amino acids after TBI but requires specialisedequipment and does not give a continuous online measureand therefore lacks the vigilance required of a clinically usefulmonitor

Inflammation Important mediators of the inflammatoryresponse have been measured in microdialysate and detected

in jugular venous (and arterial blood giving a transcranialgradient) and in CSF after TBI Analysis of the concentration

of these mediators requires offline assay and ourunderstanding of these processes is not yet at a level wheremodification of therapy (or the processes themselves) is likely

to be successful

Therefore, to date there is no CMM available with sensitivity

or specificity for an intermediate physiological variable that, ifmodified, improves outcome Such a device would requiresubsequent testing in a prospective randomised controlledtrial Current clinical management protocols aim to optimisecerebral oxygen delivery and reduce secondary insults.Therefore, we should at least monitor the endpoints of such astrategy Currently SjvO2 recording with bad-side PtiO2

monitoring is proven technology with limitations, but it iswidely available and assesses the endpoint of current intensivecare therapy after acute brain injury

Brain imaging

Brain imaging is required to identify lesions that areremediable by surgery, to aid prognosis, and to facilitate/auditclinical governance The field of imaging is advancing rapidly;blood flow and metabolism, cellular energy status, cellularrepair, occult injury, and function have all been examined

CT scanning

Marshall et al described diagnostic categories by CT scanning

that improve prognostic discrimination and permit morehomogeneous comparisons (Table 2.3) With clinical data(Traumatic Coma Data Bank, TCDB) this scale gives better

classification of “at risk” groups and has promoted thedevelopment of management guidelines, identifying subgroups

so that new therapies can be appropriately targeted and revision

of current thinking facilitated.66 Lobato et al attempted to

identify common patterns of CT change and to validate theTCDB classification through sequential CT changes, andrelating these to final outcome in severe head injurypatients.65,67,68The final outcome was more accurately predictedusing a CT scan at 48 hours than by using the initial CT scans.Because the majority of relevant CT changes developed within

48 hours after injury a pathological categorisation made byusing an early elective control CT scan seems to be most usefulfor prognostic purposes (Figure 2.1, Table 2.3)

Magnetic resonance imaging (MRI)

Diffusion weighted imaging (DWI) is a technique that can beused to probe the microenvironment of water Contrast in DWI

is derived from the translational motion of water molecules.Quantitative assessment of the (apparent) diffusion coefficient(ADCw) is a unique method of examining tissue status

In closed head injuries, focal lesions such as contusionsresulting from mechanical distortion of tissue, and haematoma,may be detected on conventional MR and CT images Diffuseaxonal injury, including axonal shearing and hypoxic braindamage, are less identifiable using such modalities Diffusionweighted and magnetisation transfer imaging sequences may

Table 2.3 Mortality by individual categories in TCDB (Traumatic Coma Data Bank) classification of brain CT Note that classes are not mutually exclusive

Imaging the brain – CT Scan Mortality (%) Diffuse injur y I (no visible lesion) 9·6

prove to be useful in highlighting axonal structural changes notobvious on T2 weighted images (Figure 2.3) With the capability

of highlighting the chemical changes that accompany suchdiffuse head injuries, MR spectroscopy has the potential todetect such disorders in vivo.69 Of particular interest is proton

MR spectroscopy at long echo times in the metabolite N-acetyl

aspartate, an amino acid found exclusively in neurons.70Usingsingle slice two dimensional spectroscopic imaging, nine acutehead injury patients and six controls have been successfullyscanned The problems presented by the need for ICUmonitoring of these patients during MR scanning wereovercome using MR compatible monitoring equipment.71 Inprevious studies of head injury which used proton spectroscopy,single voxel localisation procedures have meant that the spatialextent of the spectral data has been limited, but with spectral

Figure 2.3 Diffusion image of patient with normal CT scan of brain but persistently abnormal neurology.

The histor y of the mechanism of injur y suggests diffuse axonal injur y and there is a histor y of hypoxia and hypotension Encircled area = area with reduced ADC suggesting cellular oedema, not apparent on T2 and

CT imaging

data from a whole axial slice they have been able to identify

N-acetyl aspartate abnormalities in regions remote from any T2

visible lesions This observation suggests that spectroscopic

imaging (of N-acetyl aspartate in particular) will be useful for

the diagnosis of diffuse axonal injury It may be possible to usethis technique to guide therapy, monitor recovery, and aidoutcome prediction

Cerebral protection

Considerable effort72has gone towards the development of aneuroprotective agent, or agents, that could be given after braintrauma to reduce mortality and improve functional recovery.There have been many failed or inconclusive studies to date andthe future of pharmacological neuroprotection after TBI remains

in doubt Clinicians managing patients with a head injury aretherefore left with detection and prevention of secondary insults

to the brain, including management of medical complications ofbrain injury, and non-pharmacological interventions that mightbeneficially modify the brain’s response to trauma

Prediction of outcome

Evaluation of effectiveness of health care delivery,stratification in clinical trials, and assessment of resourceallocation requires an accurate estimator of severity of illnessand probability of hospital outcome Considerable debateexists surrounding the use of disease specific scoring systems

or a one-for-all approach The Glasgow Coma Scale (GCS) hasbeen compared with SAPS II (Simplified Acute PhysiologyScore), MPM II0, MPM II24 (Mortality Prediction Model),and APACHE II (Acute Physiology And Chronic HealthEvaluation) The GCS was not intended to be a predictor ofoutcome but was described as an assessment of depression ofconscious level Although the GCS can provide a quick guide

to the assessment of severity of injury, only a comprehensivesystem that includes the admission variables, physiologicalderangement, and age will provide accurate discriminationand prediction of outcome

McQuatt et al compared logistic regression with decision

tree analysis of an observational, head injury dataset,

including a wide range of secondary insults and 12 monthoutcomes.73 Decision tree analysis highlights patientsubgroups and critical values in variables assessed.Importantly, the results are visually informative and oftenpresent clear clinical interpretation about risk factors faced bypatients in these subgroups A decision tree was automaticallyproduced from root node to target classes based on theGlasgow Outcome Scale (GOS) score (Table 2.4).74 The mostsignificant predictors of mortality in this patient set wereduration of hypotensive, pyrexic, and hypoxaemic insults.When good and poor outcomes were compared, hypotensiveinsults and pupillary response on admission were significant.

In certain subgroups of patients pyrexia was a predictor ofgood outcome Decision tree analysis confirmed some of theresults of logistic regression and challenged others andnotably identified that brain stem reflexes are importantpredictors of outcome.75This was shown in the Glasgow–LiegeScale statistical analysis.76 Additionally the decision treeanalysis showed that GCS 3 patients often had a betteroutcome than GCS 4 patients, demonstrating that the GCS isnot a linear scale, with the GCS sum score being poor atdiscriminating between patient outcomes

The outcome after TBI can be subdivided grossly intohospital survival or death There are, however, manyfunctional outcomes among survivors Since this population

of patients is largely made up of young males, the economiccosts of survival of dependent patients is great Up to half ofall head-injured patients admitted to hospital remain disabled

at one year The combination of this factor and young agemakes the economic burden greater than in, for example,stroke Future models that predict outcome must focus uponprediction of functional outcome Factors including geneticphenotype are known to be important and will requireinclusion to achieve adequate calibration and discrimination

Rehabilitation

Brain-injured patients may benefit from advice andtreatment given by a variety of experts working as a team:neurorehabilitation physician, clinical neuropsychologist,rehabilitation nurse, physiotherapist, occupational therapist,