improving outcome after traumatic brain injury - british medical bulletin

Improving outcome after traumatic braininjury - progress and challenges

Douglas GentlemanNmewells Hospital, and Centre for Bratn Injury Rehabilitation, Royal Victoria Hospital, Dundee, UK

This article describes the rapid advances in the head injury field which havetaken place within the professional lifetime of many doctors in practice today.These have led to a better understanding of what happens in the injured brainand how these events might be manipulated to achieve better outcomes.

Clinical tools we now take for granted, like the CT scanner and the GlasgowComa Scale, were new developments 25 years ago. They provided a foundationon which clinicians and basic scientists could build what we now know: what toassess in the patient, how to respond to certain findings, what imaging to do,how to plan treatment rationally, how to minimise brain damage at differentstages after injury, how to predict and measure outcome, what disabledsurvivors need, and how to organise the service to do the greatest good for themost people. Some of these topics raise as many questions as answers.

The head injury field may be broad but it has essential unity. At one extreme,some patients have a life-threatening illness where the acts and omissions ofthe clinical team can powerfully influence not only survival but its quality. Laterthe drama of the acute phase gives way to the 'hidden disabilities' of the long-term deficits which so many survivors have. At the other end of the severityspectrum is the relatively vast number of people who suffer an apparently mildhead injury, a few of whom deteriorate and need urgent treatment, and manyof whom have unspectacular but, nevertheless, disabling problems. The articleattempts to address this broad canvas.

Clinicians, neuroscientists, policy makers, and service users must worktogether to address the major scientific, individual, and population challengesposed by head injury. Much has already been achieved, but much remains to bedone, especially in translating 'what we know' into 'what we do'.

Correspondence toMr Douglas Gentleman,

Centre for Brain InjuryRehabilitation, Royal

Victoria Hospital,Jedburgh Road,

Dundee DD2 ISP, UK

Throughout history, patients and their doctors have had good reason tofear head injury. We are fortunate to practise in an era when rapidscientific and clinical advance has enabled us to deliver outcomes whichwere well out of reach only a generation ago. However, much remainsto be discovered about the best way to treat the many ways in whichhead injury presents, and the organisation and funding of services havelagged behind scientific and clinical knowledge. This article explores the

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Improving outcome after traumatic brain injury

changes of the last 30 years, looks at why the outcome of severe headinjury has improved, discusses key issues in current research, andsuggests what could be done better with our existing knowledge.

The proverb 'everyone's business is no-one's business' sums up theorganisation of head injury care in the UK. The problem is that nomedical specialty has ownership of the problem or a monopoly ofexpertise, and the inevitable result is the collision of different and oftenantagonistic agendas.

The science of neurotrauma in the last 30 years has tended to focus onthe first hours, when life and death decisions are made and clinicians ofseveral specialties come together to manage what is often multisystemtrauma. Dramatic improvements have been seen in this phase, and thereis a good story to tell of improved outcomes1"5. However, once the patienthas been 'snatched from the jaws of death' there are more gaps in whatwe know and especially in what we do. Many of the consequences ofbrain damage remain or emerge at that stage, but rehabilitation hasattracted comparatively little attention and funding, at least in the UK.This is now changing in response to nsmg expectations of patients andtheir families, and as our growing understanding of cellular and molecularmechamsms of injury and repair allow the formulation of a more strategicapproach to head injury management6. How to restore function,independence, and quality of life to the brain injured patient is now amajor area of scientific endeavour, and clinical practice is becomingunderpinned by a steadily growing evidence base7"11.

Managing the acutely head injured patient before 1970

A generation ago, the only tools most doctors had for assessing headinjured patients were their clinical skills and plain skull films. Invasive testssuch as air encephalography and angiography were available in neuro-surgical centres, but could show only the more gross pathological changes.Management decisions had to be made with only a fraction of theinformation which is routinely available nowadays, and usually it was onlypossible to react to neurological deterioration, not to predict or prevent it.The biological basis for this deterioration was poorly understood.

There were other problems too. Few epidemiological data had ever beencollected, and there was no widely accepted way to classify head injury ormeasure its severity. In the UK at least, services for head injured patientswere fragmented and poorly co-ordinated, resources for research and forimproving clinical care were inadequate, and no specialty had taken aleadership role.

In this discouraging climate, the outcome from serious head injury wasoften dismal. To take only one example, extradural haematoma in the

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Glasgow neurosurgical unit during the period 1963-73 carried a mortal-ity of 36%. By 1988 it had fallen to 9% (Teasdale, personal communi-cation), and this was mirrored elsewhere5. What had changed?

The march of science

The anatomy of injury - imaging the injured brain

By far the most important single advance was the introduction of cross-sectional imaging of the head in the 1970s. This let the clinician see intothe brain, identify normal and abnormal structures, and plan treatmentwith confidence12-13. Although early CT scans were crude by modernstandards, this was a quantum leap forward and revolutionised headinjury management from the very start. Magnetic resonance imaging(MRI) has so far had less impact because of the practical difficulties ofgetting MR images in an acutely injured patient, but it can provide moredetail about structural brain damage14-15. This may become useful forpredicting specific residual deficits on which rehabilitative efforts can betargeted. Functional imaging, e.g. by PET scanning and SPECT scan-ning, has proved a valuable tool in neuroscience research, and may soonhave a clinical pay-off in the assessment of areas of physiological ratherthan anatomical disruption after brain injury.

The physiology of injury - measuring neurological disturbance

Clinicians need a reliable way to quantify disturbed neurological functionafter head injury, and to monitor its progress. Many local systems wereused until the 1970s, inevitably unfamiliar to outsiders, and either toocrude to detect early deterioration or too complex for general use. TheGlasgow Coma Scale (GCS)16 overcame these failings, and its world-wideadoption over the last 20 years underlines its usefulness in clinical practice.Like anything else, it only works well if those who use it are properlytrained in its use and understand its limitations17"19.

The pathology of injury - understanding events in the injured brain

Concepts of 'primary' and 'secondary' brain damage have been helpful inclinical practice for over 20 years, but it is now clear that the distinction isnot an absolute one. Electron microscopy after experimental head injuryhas shown that the ultrastructural changes of diffuse axonal injury arenot always immediately apparent20*21, and secondary brain damage can

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be the end result of biochemical and pharmacological cascades whichbegin in the brain at the moment of injury22-23.

The anatomical basis of primary brain damage is mechanicaldisruption of neurones and the cerebral micro-circulation at the time ofinjury, on a severity spectrum which ranges from simple concussion tooverwhelming - and often fatal - diffuse axonal injury24. Little can bedone to mitigate its direct effects, and this is perhaps why it has attractedless interest from clinicians than from the forensic community.Prevention has far more to offer than treatment.

Neuropathological work on fatal cases of head injury has shown howoften traumatic brain damage is the result of events which occur after thetime of injury and which may, therefore, be preventable24. Secondarybrain damage - the 'second insult' - has commanded much attention overthe last 25 years. Jennett's group described head injured patients who'talked and died', whose death was due to causes other thanoverwhelming primary bram damage25. They turned the spotlight on toraised intracranial pressure (ICP) from haematoma or bram swelling, andidentified 'avoidable factors' which had caused or contributed to thedeath of these patients: delay in evacuating haematomas; uncontrolledintracranial infection or epilepsy; and failure to correct systemic hypoxia,hypercarbia, and shock26"28. Other groups have since re-inforced thesefindings in different geographical settings and patient groups29"33.

The aim is to define what should and should not be done in the earlyhours and days after injury in order to optimise outcome. It is now wellunderstood that the final common pathway for secondary brain damageis an inadequate oxygen supply to the injured brain, often associatedwith reduced cerebral blood flow and a rise in ICP34. Mechanicallyinjured neurones are highly susceptible to hypoxic-ischaemic damage,and the depth and duration of the insult determine the extent andreversibility of this damage35'36. Technical advances in monitoringtechniques have only served to underline the fundamental role of afailing oxygen supply in causing neuronal loss after trauma37"39.

The biochemistry of injury - analysing the chemical environment

The last decade has seen an explosion in our understanding of thebiochemical cascades which follow brain injury. Injured neurones can befurther compromised by the action of molecules and ions in theirimmediate environment. Depolarisation by excitotoxic neurotransmitters,degradation of phospholipid membranes, inflammatory tissue changes,and disruption of the regulatory mechanisms for trans-membrane sodiumand calcium ion transport can all deliver the coup de grace to injuredneurones and worsen clinical outcome22"23-40'41.

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More positively, a better understanding of these processes has led to avigorous search for 'neuro-protective' drugs to prevent or limit this type ofsecondary brain damage at the cellular level42'43. Unfortunately, promisingresults in animal studies and preliminary clinical studies have beenfollowed by disappointing results from almost all clinical trials carried outso far44"48. There is some good news: the calcium channel blocker nimo-dipine (used for over a decade in aneurysmal subarachnoid haemorrhage)benefits patients with traumatic subarachnoid haemorrhage too49, andencouraging results have also been obtained from the use of gangliosidesand steroids in spinal cord injury50*51. Perhaps head injury is too hetero-geneous a condition to be much affected by drugs with a single mechanismunder the conditions of a randomised controlled trial.

The cell biology and molecular biology of injury - how the brain repairs itself

Animal experiments, tissue culture techniques, and electron microscopyhave taught us much about the mechanisms of structural repair in theinjured brain and their functional significance52"55. We are also starting toglimpse how these might be manipulated. For example, grafting peri-pheral nerves into the brain can alter the cellular micro-environment in away which favours axonal regrowth and new synapse formation50'56.Neurotrophins can stimulate neuronal and glial activity, up-regulate theproduction of antioxidant enzymes, and attenuate cell death inexperimental models of cerebral ischaemia. Difficulties of delivering thedrug to the brain may eventually be overcome by chemically linking it topolyethylene glycol and a monoclonal antibody to promote receptor-mediated transport across the blood-brain barrier57. Unfortunately thevalue of some potential treatments (e.g. antibodies to cytokines such asinterleukin) may be undermined by their interference with beneficial aswell as harmful effects58.

Translating scientific progress into clinical practice - how farhave we got?

The common thread from all clinical and pathological studies of headinjury over the last 30 years is that secondary brain damage is commonand usually preventable by clinical or organisational means. Often it canbe traced to delay in the evacuation of a significant intracranialhaematoma, or failure to correct systemic cardio-respiratory com-promise. How to minimise these 'second insults' to the brain throughoptimal organisation of services and care of individuals is the mainclinical challenge in head injury59.


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Finding and treating intracranial lesions

The advent of CT scanning revolutionised head injury practice byallowing treatable lesions13'60 - especially haematomas - to be diagnosedbefore cascades of intracranial events cause physiological 'meltdown'.One consequence was that many patients were found to be harbouringclinically silent lesions which caused delayed deterioration, with only asmall window of opportunity to prevent this becoming a point of noreturn61"63. Good practice now demands that decisions about where tocare for a patient are informed by early knowledge of what structuralpathology is present in the brain.

Less than 0.5% of head injured hospital attenders need a neurosurgicaloperation, usually for haematoma64'65, but it is essential to have a triagetool which reliably identifies them. In both adults and children, anabnormal conscious level and a skull fracture are powerful and additivepredictors of haematoma, and define a high risk group needing urgent CTscan66'67. At first, the scarcity of scanners meant that a decision to do ascan was usually the same as referral to a neurosurgeon, and led to a greatincrease in the number of high risk patients transferred urgently toneurosurgical units for a scan60. The consequences for the safety oftransfer are considered later.

Nowadays almost every accident and emergency department in the UKhas easy access to a scanner, at least during working hours68, and theinformation from these can aid the decision-making process. Patients nolonger need to travel to a neurosurgical unit simply for diagnosis, but iftransfer is indicated on clinical grounds anyway it may be quicker andmore convenient to do the scan on arrival at the neurosurgical unit.

Imaging mildly head-injured patients - are some lesions incidental?

Many patients with less severe head injuries (as judged by earlyphysiological and neurological disturbance) nevertheless go on todevelop residual physical and especially neuropsychological deficitswhich affect their health and function in the longer term69"72. There isgrowing interest in how these patients can be identified, and in thepossible benefits of follow-up and rehabilitation10'73'74).

The history of imaging after head trauma shows that ever more lesionsare diagnosed as better resources and growing demand progressivelylower the threshold for CT scan. A few patients certainly deteriorate as theresult of intracranial complications after apparently minor head injury75"79.In healthcare systems with high public expectations and intolerance ofclinical misjudgement this becomes an important driver of clinical policy.

There are of course well-known traps for the unwary in the manage-ment of mild head injury: drunks61'80, children81, and the elderly82. Beyond


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these categories the traditional tools of clinical assessment and plain skullradiology have found a new lease of life in the triage of mildly headinjured patients to select those who merit a CT scan83"85.

Standard UK practice is now rapidly evolving to the point where anypersistent alteration of conscious level (or other neurological symptomor sign) warrants a CT scan in a general hospital, even if it is likely thatno surgically significant lesion will be found. This has already becomewidespread practice in North America and much of continentalEurope75-84-8*^90. There is also growing interest in holistic approaches toassessing and managing the head injury workload of a region83-91.

An obvious question is whether some types of intracranial pathologycan safely be ignored. Discovering a small haematoma or contusion maynot alter clinical management in the acute stage, but finding a lesionshould increase the care with which the patient is monitored, and raisethe index of suspicion for any changes in their clinical condition. Giventhe scarcity and uneven distribution of rehabilitation services in the UKfinding a lesion may also alter decisions about follow-up assessment todetect and treat residual deficits. MR imaging detects far more lesionsthan CT scanning14-15-92, and if it becomes more widely used in the acute(or post-acute) investigation of minor head injury this will haveimplications for the number of such patients referred to head injuryclinics and rehabilitation services.

Monitoring the patient with a serious brain injury

Another dilemma has been how to decide whether a particular haema-toma needs to be evacuated. Monitoring ICP can identify those at risk ofneurological deterioration and allow pre-emptive intervention93. Fluid-phase monitoring usmg a ventricular catheter is cheap but prone tomalfunction, and single use high fidelity solid state transducers are nowavailable (at a price). Despite much enthusiasm for ICP monitoring overthe years there is no evidence that lowering ICP by pharmacological orother means improves outcome after head injury. Perhaps high ICP is justan epiphenomenon, and to focus on lowering it is to miss the patho-physiological point.

ICP monitoring seems to be of greatest use when linked to otherphysiological data to derive variables such as cerebral perfusion pressureand cerebral oxygen extraction94. Technical advances now allow theautomated collection and integration of data in neurosurgical ITUs,which through servo systems can be used to regulate ventilatory para-meters or drug infusion as a form of artificial homeostasis37. Therationale is that on-line correction of physiological abnormalities canprevent or limit secondary brain damage and improve outcome,


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especially in an unstable patient, although this has yet to be proved.Such systems require a high level of clinical and technical support, andmore work needs to be done to establish their place in clinical practice.

Resuscitation and transfer

Hypoxaemia, hypercarbia, and hypovolaemic shock are potent causes ofavoidable death and disability after injury, independent of the patient'sconscious level and the CT scan findings4'32"33'95.

Some complications of head injury carry a high risk of hypoxaemiaand hypercarbia: uncontrolled seizures, inadequate breathing, andobstruction of the airway by vomit, blood, or dentures28. The risk to theairway is closely related to the patient's conscious level, and it is nowwidely accepted that the only effective way to protect the airway in apatient who is unconscious (or nearly so) is endotracheal intubation andventilation using sedative or paralysing drugs.

In patients with a seriously altered conscious level the airway canbecome obstructed at any time - accident scene, ambulance, accident andemergency department, ward, or neurosurgical unit. Oxygenation must beguaranteed at every stage. Bringing the doctor or paramedic to the sceneof the accident can secure the airway early on, but it is now generallyaccepted that a severely injured patient cannot be fully stabilised in thefield. Military experience has taught valuable lessons; in all recent wars aseriously injured soldier's interests have been best served by rapidevacuation to a field hospital after life-saving interventions96-97 and incivilian practice the same principle holds true. The US and Germany havedeveloped trauma systems based on networks of designated traumacentres and fast transport98"101, whereas the UK system is still based onlocal hospitals - most with no neurosurgical unit on site. However, recentcontroversial data suggest that the 'macro-organisation' of the traumaservice may matter less than the quality of care at the 'micro-level' - theindividual clinician and team102.

Seriously head injured patients remain liable to airway obstruction andhypoxaemia after arrival at hospital, especially when moved betweendepartments or taken to another hospital for CT scanning or specialisttreatment103. Complications often follow sub-optimal management of theairway before and during transfer to the neurosurgical unit4, andrecognition of this has led to improved airway care and arrangements fortransfer, and improved outcomes, although shortcomings persist104'105.

Victims of high velocity injuries such as road accidents and falls froma height often suffer serious blood loss from major extracranial injuries.These can be surprisingly hard to detect in the head injured patient,especially if unconscious and unable to complain of pain106-107. To miss


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or underestimate these injuries puts the patient at substantial risk ofhypovolaemic shock and secondary brain damage95-108.

A pro-active and systematic approach to assessment is needed -clinical examination of every part of the body by an experienced doctor,focused use of radiography and other investigations, and a high index ofsuspicion when seeking injuries (especially with ongoing cardiovascularinstability). To underestimate a serious extracranial injury can be asserious as to miss it, and undue haste in sending an unconscious patientto the neurosurgical unit or the CT scanner can result in inadequate fluidresuscitation or a failure to stop bleeding before transfer. The surgicalcontrol of thoracic or abdominal haemorrhage can be a higher prioritythan the head injury itself.

The introduction of Advanced Trauma Life Support (ATLS) courses inthe US in 1980 and the UK eight years later systematised organisationand early management. ATLS promotes a uniform method of assess-ment, a clear order of priorities in resuscitation, the principle of 'do nofurther harm', and an emphasis on the benefits of early surgicalinvolvement in trauma care109. The lack of randomised controlled trialsmakes it hard to show scientifically conclusive evidence that ATLS hasimproved outcomes. However, in the UK the 'early' peak in the trimodaldistribution of deaths after trauma has been largely eliminated110,suggesting that the quality of early care has improved. Victims of injurynow die either at once (perhaps inevitably) or else later in the ITU frommulti-organ failure, suggesting that new educational practices have hadpositive clinical results.

Guidelines in head injury practice

The 'guidelines movement' in medicine has recently emerged as part ofa drive for evidence-based practice. Guidelines are not rigid protocolsand do not replace clinical judgement, but provide a framework withinwhich it can be exercised safely. Guidelines for managing seriously headinjured patients were first formalised in the UK in the 1980s66, and werebased on evidence that timely transfer to neurosurgery would reduce thenumber of haematoma patients who deteriorated into coma beforesurgery, and would lower mortality and morbidity60. New or updatedguidelines are emerging from the UK111, Scotland85, Europe112, andNorth America113, to take account of new scientific and clinical know-ledge and changes in facilities and in expectations.

Different groups tend to focus on different problems and theirrecommendations can seem confusingly different. One solution is a multi-specialty or multi-professional approach to the development of guidelines,based on the best possible evidence available from the literature or from

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expert opinion. Those who have been through this process are well awarehow few rigorous scientific studies exist in the head injury field, partlybecause of practical difficulties in devising such studies. Recommend-ations then have to be made on the basis of less robust evidence such asobservational studies and expert opinion. There are also concerns aboutwhether guidelines are actually put into practice114. The challenge over thenext few years will be not just to devise guidelines but to make thempragmatic and acceptable to those who have to adapt them to everydayclinical practice within their local circumstances.

Epidemiology and organisation of head injury care in the UK

Head injury is extremely common, whether isolated or as part of multi-system trauma65'115-116. Epidemiological studies 20 years ago suggestedthat about a million people attend UK hospitals each year after a headinjury64, and there seems no reason to believe that this has changed.Most have had a minor head injury and can go home after first aid, butwe need to be able to identify the 10-15% who have (or may have had)a brain injury and who must be admitted to hospital for observation ortreatment.

Where they should go? In the UK as a whole only around 1% ofhospital attenders are transferred to a neurosurgical unit, and widelydifferent bed-population ratios provide indirect support to the anecdotalbelief that practice varies around the country. Clearly everyone should betransferred whose injury may need a neurosurgical operation, but that isperhaps only 3% of those admitted to hospital. This raises importantquestions about the management of the others. Should an unconsciouspatient with a proven diffuse brain injury be admitted to a general ITUwhich has limited facilities for intracranial monitoring, or to a neuro-surgical unit despite the absence of need for operative intervention? Is itreasonable to admit someone with a moderately altered conscious leveland scattered contusions to a general surgical or orthopaedic ward forclinical 'observation'? What is observation anyway?

Where head injured patients should be taken, when and how theyshould get there, and what staff and facilities should be awaiting them,are still live issues117"120. The recent report on the organisation of headinjury care from The Royal College of Surgeons of England121 is unlikelyto be the last word on a subject which inevitably affects a number ofspecialties. Its recommendation that more head injured patients should becared for in accident and emergency medicine and neurosurgery, and fewerin general and orthopaedic surgery, is proving predictably controversial.This would require the re-allocation of existing resources and would havemajor implications for training and manpower.

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Rehabilitation

Earlier in this chapter evidence was presented to support the concept thatbrains which have sustained sub-lethal doses of injury have some capacityto restore neuronal connections and function if the subsequent micro-environment is supportive rather than hostile. Mechanisms includeneuronal plasticity, unmasking of latent pathways, differentiation of stemcells into neurones and gha, support of injured neurones by glia, and up-regulation of antioxidant enzymes and neurotrophins122-123. Therapeutictrials have generally sought to mimic the action of endogenous com-pounds using drugs or implants: neurotrophins124, gangliosides50, orneurotransmitters125'126. Promising results from the laboratory and fromearly clinical studies offer a biological rationale for providing maximumcare to support the severely injured brain until the acutely disturbedphysiology starts to stabilise, then embarking on a rehabilitation pro-gramme aimed at restoring maximum function and independence.

In an ideal world, rehabilitation would be a concept or process whichpermeated all therapeutic endeavours after head injury, not a medicalspecialty or an activity done at a particular place. Practical conside-rations dictate that specialist units are necessary to concentrate scarceexpertise and to provide an appropriate therapeutic environment. Thereare far too few brain injury rehabilitation services in the UK, and accessto them is variable and can appear to reflect 'post-code medicine'.Evidence suggests that most British head injured patients have no accessto any organised rehabilitation process, such as accurate informationabout head injury, a multi-professional assessment of their needs, orspecialist therapists or clinical neuropsychologists127"129. This is despiteclear evidence from different types of study that the neuropsychologicaland psychosocial sequelae of traumatic brain injury are extremelycommon, have pervasive and persistent adverse effects (even after a'good' neurological recovery), and need skilled intervention130"133.

Data from several countries, including the UK, have shown as con-clusively as will ever be possible that organised rehabilitation pro-grammes are beneficial to the seriously brain injured patientW1'134'135.Insurance funders in the US are prepared to spend money up front inorder to save money later, and one study has suggested that their outlayis recouped within 3 years through reduced care bills8. Recent evidencesuggests that systematic follow-up after head injury reduces socialmorbidity and the severity of post-concussional symptoms10. There aremany models for brain injury rehabilitation, the details of which arebeyond the scope of this article. Most are based on goal setting andachievement and use an interdisciplinary approach. Unfortunately,resource and specialist staffing are major limiting factors for the sorelyneeded expansion of rehabilitation facilities in the UK.


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Auditing process and outcome

As clinical innovation has matured into respectable clinical practice theemphasis has begun to shift towards auditing process and outcome136.Perhaps the aim is to reassure ourselves and others that we are doing ourbest, but audit can also demonstrate the local variability in the qualityof trauma care. Greater governmental and public scrutiny of hospitalservices in the coming years is likely td yield interesting findings aboutvariations in the organisation and quality of trauma care.

The future

Preventing secondary brain damage after head injury poses organisationaland scientific challenges. The treatment of seriously injured patients in theaccident and emergency department is no longer routinely left to the leastexperienced doctors without supervision - a professional response tobetter data and to rising public expectations of the standard of care.However, given the fast turnover of junior medical staff, the education ofthose who treat the injured must be a constant propaganda exercise.Guidelines can help doctors and nurses know what to do in a given set ofcircumstances.

The head-injured patient presents a multi-speciality and multi-professional problem. There is an urgent need for more consultants inneurosurgery and general surgery to take an interest in trauma, and formore therapists and clinical psychologists to work in neurotraumarehabilitation. The UK National Health Service culture of recent years hasunwittingly contributed to a tendency to regard trauma patients as anuisance and an obstacle to the proper business of treating electivepatients. Some head injured patients, notably those with a severe diffuseinjury and those with mild or moderate injuries, continue to have aparticularly raw deal. The limited resources for developing trauma careand for research also tend to dampen professional enthusiasm forinnovation and improvement.

The quest for the holy grail of a neuro-protective drug againstsecondary brain damage has so far proved as fruitless as the Arthurianoriginal, but perhaps the journey is as important as the arrival. What welearn from these studies informs us greatly about processes which takeplace m the injured brain. Our challenge is to match our treatments tothese processes, and it is probably safe to predict that in the next 20years many exciting developments will further improve outcome afterbrain injury.


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References

1 Becker DP, Miller JD, Ward JD, Gienberg R, Young HF, Sakalus R The outcome from severehead injury with early diagnosis and intensive management / Neurosurg 1977; 47: 491-502

2 Bncolo AP, Pasut LM. Extradural hematoma toward zero mortality. A prospective study.Neurosurgery 1984; 14 8-12

3 Klauber MR, Marshall LF, Toole BM, Knowlton SL, Bowers SA Cause of decline in head-in|ury mortality rate in San Diego County, California. J Neurosurg 1985; 62: 528-31

4 Gentleman D. Causes and effects of systemic complications among severely head injuredpatients transferred to a neurosurgical unit. Int Surg 1992; 77: 297-302

5 Jones NR, Molloy CJ, Kloeden CN, North JB, Simpson DA. Extradural haematoma: trends inoutcome over 35 years Br ) Neurosurg 1993, 7: 465-71

6 Teasdale GM, Graham DI. Craruocerebral trauma: protection and retrieval of the neuronalpopulation after injury. Neurosurgery 1998; 43- 723—37

7 Cope DN, Hall KA. Head injury rehabilitation: benefits of early intervention. Arch Pbys MedRehab 1982, 63: 433-7

8 Aronow HU Rehabilitation effectiveness with severe brain injury: translating research intopolicy. J Head Trauma Rehab 1987, 2: 24-36

9 Brooks N. The effectiveness of post-acute rehabilitation. Brain Injury 1991, 5: 103-910 Wade DT, King NS, Wenden FJ et al. Routine follow-up after head injury a second randomised

controlled trial ] Neurol Neurosurg Psychiatry 1998, 65: 177-8311 Semlyen JK, Summers SJ, Barnes MP Traumatic brain injury efficacy of multidisciphnary

rehabilitation. Arch Phys Med Rehab 1998, 79: 678-8312 Ambrose, J, Gooding M, Uttley D. EMI scan in the management of head injuries Lancet 1976;

i 847-813 French BN, Dublin AB. The value of computerised tomography in the management of 1000

consecutive head ui)unes Surg Neurol 1977; 7: 171-8314 Hadley DM, Teasdale GM, Jenkins A et al Magnetic resonance imaging in acute head injury.

Clm Radiol 1988; 39: 131-915 Mittl RL, Grossman RI, Hiehle JF et al. Prevalence of MR evidence of diffuse axonal injury in

patients with mild head injury and normal head CT findings Am J Neurol Rad 1994, 15:1583-9

16 Teasdale GM, Jennett B Assessment of coma and impaired consciousness. Lancet 1974, u: 81—417 Teasdale G, Knill-Jones R, Van der Sande J. Observer variability in assessing impaired

consciousness and coma. / Neurol Neurosurg Psychiatry 1978, 41: 603-1018 Morns K Assessment and communication of conscious level: an audit of neurosurgical

referrals. ln]ury 1993; 24 369-7219 Prasad K The Glasgow Coma Scale: a critical appraisal of its clinimetnc properties. / Cltn

Epidemiol 1996; 49 755-6320 Povlishock JA, Christman (JW The pathobiology of traumatically induced axonal injury in

animals and humans: a review of current thoughts. / Neurotrauma 1995; 12: 555—6421 Maxwell WL, Povlishock JT, Graham DI. A mechanistic analysis of non-disruptive axonal

in|ury: a review. / Neurotrauma 1997, 14: 419—4022 Katayama Y, Becker DP, Tamura T, Hovda DA. Massive increases in extracellular potassium

and the indiscriminate release of glutamate following concussive brain in|ury. / Neurosurg1990, 73: 889-900

23 Faden Al, Demediuk P, Panter SS et al. The role of excitatory amino acids and NMDA receptorsin traumatic brain in)ury Science 1989; 244. 798-800

24 Adams JH. The neuropathology of head in)unes In Vinken PJ, Bruyn G (Eds) Handbookof Clinical Neurology, Vol 23 Amsterdam: North Holland, 1975; 35

25 Reilly PL, Adams JH, Graham DI, Jennett B. Patients with head injury who talk and die. Lancet1975, ii: 375-7

26 Rose J, Valtonen S, Jennett B. Avoidable factors contributing to death after head in|ury. BMJ1977, ii: 615-8

27 Jennett B, Carlin J. Preventable mortality and morbidity after head in)ury Injury 1978; 10: 31-928 Gentleman D, Jennett B Hazards of inter-hospital transfer of comatose head injured patients

Lancet 1981, u 853-529 Miller JD, Sweet RC, Narayan RK, Becker DP. Early insults to the injured brain. JAMA 1978;

240: 439-42

922 British Medial Bulletin 1999,55 (No 4)

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30 Sharpies PM, Storey A, Aynsley-Green A, Eyre J. Avoidable factors contributing to death ofchildren with head injuries. BMJ 1990; 300: 87-91

31 Lobato RD, Rivas JJ, Gomez PA et al Head injured patients who talk and deteriorate intocoma. / Neurosurg 1991; 75: 256-61

32 Chesnut RM, Marshall LF, Klauber MR et al The role of secondary brain injury in determiningoutcome from severe head injury. / Trauma 1993; 34: 216-22

33 Wald SL, Shackford SR, Fenwick J The effect of secondary insults on mortality and long termdisability after severe head injury in a rural region without a trauma system. / Trauma 1993,34. 377-81

34 Miller JD, Becker DP. Secondary insults to the injured brain / R Coll Surg Edinb 1982, 27: 292-835 Ishige N, Pitts LH, Hashimoto T, Nishimura MC, Bartkowski HM. Effect of hypoxia on

traumatic bram injury in rats Neurosurgery 1987; 20: 848-5336 Jenkins LW. Increased vulnerability of the traumatised brain to early ischemia In- Baethmann

A, Go GK, Unterberg A (Eds). Mechanisms of Secondary Bram Damage New York: Plenum,1986

37 Jones PA, Andrews PJ, Midgley S et al. Measuring the burden of secondary insults in headinjured patients during intensive care / Neurosurg Anesth 1994; 6: 4-14

38 Bardt TF, Unterberg AW, Harth R, Kiemng KL, Schneider GH, Lanksch WR. Monitoring ofbrain tissue pO2 in traumatic brain injury: effect of cerebral hypoxia on outcome. AdaNeurochir Wien Suppl 1998; 71- 153-6

39 Bardt TF, Unterberg AW, Kiemng KL, Schneider GH, Lanksch WR. Mulnmodal cerebralmonitoring in comatose head-injured patients. Acta Neurochir Wten 1998; 140 357-65

40 Chan PH, Yurko M, Fishman RA Phosphohpid degeneration and cellular edema induced byfree radicals in bram cortical slices. / Neurochem 1982; 38: 525-31

41 Holmin S, Soderlund J, Biberfeld P, Mathieson T. Intracerebral inflammation after human bramcontusion Neurosurgery 1998; 42 291-8

42 Mclntosh TK Novel pharmacologic therapies in the treatment of experimental traumatic braininjury: a review. / Neurotrauma 1993, 10: 215-61

43 Bullock R Opportunities for neuroprotective drugs in clinical management of head injury. /Emerg Med 1993, 11 (Suppl 1): 23-30

44 Alderson P, Roberts I Corticosteroids in acute traumatic brain injury: systematic review ofrandomised controlled trials BMJ 1997, 314 1855-9

45 Langham J, Goldfrad C, Teasdale GM, Shaw D, Rowan K Assessing the effects of calciumchannel blockers in patients with acute traumatic brain in)ury on mortality and neurologicaldisability (Cochrane Review) In Cochrane Library, Issue 3, London: Update Software, 1998

46 Marshall LF, Maas AIR, Marshall SB et al A mulncentre trial on the efficacy of using tinlazadmesylate in cases of head injury. / Neurosurg 1998, 89 519-25

47 Morns GF, Bullock R, Marshall SB, Marmarou A, Maas A, the Selfotel Investigators, MarshallLF Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS-19755) in thetreatment of severe head injury: results of two Phase III trials. / Neurosurg 1999, 91: 737-43

48 Marion DW, Penrod LE, Kelsey SF et al. Treatment of traumatic brain in|ury with moderatehypothermia. N Engl] Med 1997, 336. 540-6

49 Harders A, Kakaneka A, Braakman R, and the German Subarachnoid Haemorrhage StudyGroup Traumatic subarachnoid hemorrhage and its treatment with nunodipine. / Neurosurg1996; 85- 82-9

50 Gono A Gangliosides as a possible treatment affecting neuronal repair processes. Adv Neurol1988; 47 523-30

51 Bracken MB, Shepard MJ, Collins WF et al. A randomised controlled trial ofmethylprednisolone or naloxone in the treatment of acute spinal cord injury results of theSecond National Acute Spinal Cord Injury Study N Engl] Med 1990; 322. 1405-11

52 Steward O. Assessing the functional significance of lesion-induced neuronal plasticity. Int RevNeurobiol 1982; 23: 197-254

53 Bower AJ. Plasticity in the adult and neonatal central nervous system. Br J Neurosurg 1990, 4:253-64

54 Blight AR. Containing plasticity: neunte inhibitory factors of myehn. Nat Neurosct 1998. 1:87-8

55 Fitzpatnck MO, Dewar D, Teasdale GM, Graham DI. The neuronal cytoskeleton in acute brainui|ury. Br ] Neurosurg 1998; 12: 313-7

56 David S, Aguayo AL. Axonal elongation into peripheral nervous system 'bridges' after central


Dow


ic.oup.com/bm


ber 2018

Trauma

nervous system injury in adult rats. Saence 1981, 214: 93157 Wu D, Pardndge WM. Neuroprotection with non-invasive neurotrophin delivery to the brain.

Proc Natl Acad Sa USA 1999, 96 254-9958 Guilian D, Vaca K, Corpuz M. Brain glia release factors with opposing actions upon neuronal

survival. / Neurosci 1993, 13: 29-3759 Gentleman D Preventing secondary brain damage after head injury: a multidisciplinary

challenge. Injury 1990, 21: 305-860 Teasdale G, Galbraith S, Murray L, Ward P, Gentleman D, McKean M. Management of

traumatic intracranial haematomas. BMJ 1982; 285: 1695-761 Galbraith S Misdiagnosis and delayed diagnosis in traumatic intracranial haematoma. BMJ

1976; i: 1438-962 Mendelow AD, Karmi MZ, Paul KS, Fuller GAG, Gillingham FJ. Extradural haematoma: effect

of delayed treatment BMJ 1979, i 1240-263 Seehg JM, Becker DP, Miller JD, Greenberg RP, Ward JD, Choi SC. Traumatic acute subdural

haematoma- major mortality reduction in comatose patients treated within four hours N EnglJ Med 1981, 304: 1511-8

64 Jennett B, MacMdlan R. Epidemiology of head injury BMJ 1981; 282- 101-465 Jennett B Epidemiology of head injury. / Neurol Neurosurg Psychiatry 1996; 60 362-966 Bnggs M, Clarke P, Crockard A et al. Guidelines for initial management after head injury in

adults: suggestions from a group of neurosurgeons. BMJ 1984, 288: 983-567 Teasdale GM, Murray G, Anderson E, Mendelow AD, MacMiUan R, Jennett B. Risks of acute

traumatic mtracranial haematoma in children and adults: implications for managing headinjuries. BMJ 1990; 300 363-7

68 MacNamara AF, Evans PA. The use of CT scanning by accident & emergency departments inthe UK. past, present, and future Injury 1995; 26. 667-9

69 Rimel RW, Giordani B, Barth JT, Jane JA. Moderate brain injury: completing the clinicalspectrum of brain trauma. Neurosurgery 1982; 11 344-51

70 Lowden IMR, Bnggs M, Cockin J. Post-concussional symptoms following minor head injury.Injury 1989, 20: 193-4

71 Middleboe T, Anderson HS, Birket-Smith M, Frns ML. Minor head injury impact on generalhealth after 1 year. A prospective follow-up study. Acta Neurol Scand 1992, 85: 5-9

72 Stablum F, Mogentale C, Umilta C. Executive functioning following mild closed head injury.Cortex 1996; 32: 261-78

73 Hodgkinson D, Berry E, Yates DW. Mild head injury - a positive approach to management. EurJ EmergMed 1994, 1:9-12

74 Gentleman D Rehabilitation and the neurosurgeon. Br J Neurosurg 1996, 10: 537—4075 Servadei F, Faccani G, Roccella P et al. Asymptomatic extradural haematomas: results of a

multicentre study of 158 cases in minor head injury. Acta Neurochtr Wien 1989; 96 39-4576 Miller JD, Murray LS, Teasdale GM. Development of a traumatic intracranial haematoma after

a 'minor' head injury Neurosurgery 1990; 27: 669-7377 Stein SC, Ross SE. The value of computed tomographic scans in patients with low-nsk head

injuries. Neurosurgery 1990; 26: 638-4078 Lee ST, Liu TN, Wong CW, Yeh YS, Tzaan WC. Relative risk of deterioration after mild closed

head injury. Acta Neurochir Wun 1995; 135: 136-4079 Hsiang JNK, Yeung T, Yu ALM, Poon WS. High-risk mild head injury. / Neurosurg 1997; 87

234-880 Cook LS, Levitt DO, Simon B, Williams VL. Identification of ethanol-intoxacated patients with

minor head trauma requiring computed tomography scans. Acad Emerg Med 1994; 11 227-3481 Casey R, Ludwig S, McCormick MC. Morbidity following minor head trauma in children.

Pediatrics 1986; 78: 497-50282 Roy CW, Pentland B, Miller JD The causes and consequences of minor head injury in the

elderly. Injury 1986, 17: 220-383 Servadei F, Vergoni G, Nasi MT, Staffa G, Donati R, Arista A Management of low-nsk head

injuries in an entire area- results of an 18 month survey. Surg Neurol 1993, 39: 269-7584 Miller EC, Derlet RW, Kinser D. Minor head trauma is CT always necessary? Ann Emerg Med

1996; 27: 290-485 Scottish Intercollegiate Guidelines Network. Guidelines on the early management of acute head

injury Edinburgh: SIGN, 2000: In press86 Dacey RG, Alves W, Rimel R et al. The risk of serious neurosurgical complications after


Dow


ic.oup.com/bm


ber 2018


apparently minor head injury. / Neurosurg 1986, 65 203—1087 Jeret JS, Mandell M, Anziska B et al. Clinical predictors of abnormality disclosed by computed

tomography after mild head trauma. Neurosurgery 1993; 32 9-1688 Pitts LH. The role of neuroimaging in minor head injury. Ann Etnerg Med 1991; 20: 1387-889 Shackford SR, Wald, S, Ross SE et al. The clinical utility of computed tomographic scanning

and neurologic examination in the management of patients with minor head injuries / Trauma1992; 33: 385-94

90 Stein SC, Ross SE. Mild head injury a plea for routine early CT scanning. / Trauma 1993; 33:11-3

91 King NS, Wenden FJ, Wade DT. Interventions and service need following mild and moderatehead injury: the Oxford head injury service. Clin Rehab 1997; 11: 13-27

92 Yokota H, Kurokawa A, Otsuka T, Kobayashi S, Nakazawa S. Significance of magneticresonance imaging in acute head injury./ Trauma 1991, 31- 351-7

93 Teasdale G, Galbraith S, Jennett B. Operate or observe' ICP and the management of the 'silent'traumatic intracranial haematoma. In Shulman K, Marmarou A, Miller JD et al (Eds),Intracranial Pressure IV. Berlin: Springer, 1980

94 Mathew P, Gentleman D, Bullock MR. Brain monitoring in severe head injury: a practicalguide. Trauma 1999; 1: 105-14

95 Anderson ID, Woodford M, de Dombal FT, Irving M Retrospective study of 1000 deaths frominjury in England and Wales. BMJ 1988, 296 1305-8

96 Pfeffermann R, Rozin RR, Durst AL, Mann G. Modern war surgery: operations in anevacuation hospital during the October 1973 Arab-Israeli war. / Trauma 1976; 16: 694-703

97 Jevtic M, Petrovic M, Ignjatovic D et al. Treatment of wounded in the combat zone. / Trauma1996, 40 (Suppl 3) S173-6

98 AJlgower M. Trauma systems in Europe Am J Surg 1991; 161 226-999 Regel G, Lobenhoffer P, Grotz M, Pape HC, Lehmann U, Ifscherne H. Treatment results of

patients with multiple trauma an analysis of 3406 cases treated between 1972 and 1991 at aGerman Level I Trauma Centre / Trauma 1995, 38 70-8

100 Pitts LH Neurotrauma and trauma systems. New Hortz 1995; 3: 546-8101 Bazzoh GJ, Madura KJ, Cooper GF, Mackenzie EJ, Maier RV. Progress in the development of

trauma systems in the United States: results of a national survey JAMA 1995, 273- 395-401102 Nichol J, Turner J. The effectiveness of a regional trauma system in reducing mortality from

major trauma: before and after study. BMJ 1997, 315- 349-54103 Andrews PJD, Pif>er IR, Dearden NM, Miller JD Secondary insults during intrahospital

transport of head-injured patients. Lancet 1990, 335: 327-30104 Vyvyan HAL, Kee S, Bnstow A. A survey of secondary transfers of head injured patients in the

south of England Anaesthesia 1991; 46: 395-7105 Lambert SM, Wdlett K. Transfer of multiple injured patients for neurosurgical opinion- a

study of the adequacy of assessment and resuscitation. Injury 1993; 24. 333-6106 McLaren CAN, Robertson C, Little K. Missed orthopaedic injuries in the resuscitation room.

/ R Coll Surg Edinb 1983; 28: 399^(01107 Gentleman D, Teasdale G, Murray L Cause of severe head injury and risk of complications.

BMJ 1986; 292: 449108 Pick J, Chesnut RM, Marshall LF et al. Extracrarual complications of severe head injury /

Neurosurg 1992, 77 901-7109 American College of Surgeons Committee on Trauma ATLS Course Manual Chicago:

American College of Surgeons, 1997110 Wyatt J, Beard D, Gray A, Busuttil A, Robertson C. The time of death after trauma. BMJ

1995; 310- 1502111 Bartlett J, Kett-White R, Mendelow AD, Miller JD, Pickard J, Teasdale G. Guidelines for the

initial management of head injuries: recommendations from the Society of British NeurologicalSurgeons. Br J Neurosurg 1998; 12: 349-52

112 Maas AIR, Dearden NM, Teasdale GM et al EBIC guidelines for management of severe headinjury in adults Acta Neurochtr Wien 1997; 139: 286-94

113 Bullock R, Chesnut R, Clifton G et al. Guidelines for the management of severe head ui|ury.EurJ Emerg Med 1996; 3: 109-27

114 Gentleman D, Seex K, Ritchie D Outcome from acute traumatic intracranial haematoma:application of guidelines in pre-neurosurgical management Acad Emerg Med 1994; 1: 305-6

115 Goldstein M. Traumatic brain injury: a silent epidemic Ann Neurol 1990, 27: 327

British Medical Bulletin 1999,55 (No 4) &25

Dow


ic.oup.com/bm


ber 2018

Trauma

116 Kraus JF Epidemiology of head injury In: Cooper PR (Ed) Head Injury Oxford: Willons, 1993117Teasdale G. Head injuries are badly managed in accident and emergency departments and

neurosurgeons are partly to blame Arch Emerg Med 1984; 3: 123-34118 Gentleman D, Dearden M, Midgley S, Maclean D. Guidelines for the resuscitation and transfer

of patients with serious head injury. BMJ 1993; 307: 547-52119 Munro HM, Laycock JRD. Inter-hospital transfer: standards for ventilated neurosurgical

emergencies. Br ] Intensive Care 1993, 3 210—4120 Jenkinson JL, Saunders DA, Wallace P, Gentleman D, Francis G, Bnstow A. Recommendations

for the transfer of emergency head injured patients to neurosurgical centres. London:Neuroanaesthesia Society/Association of Anaesthetists, 1997

121 Royal College of Surgeons of England. Report of the Working Party on the Management ofPatients with Head Injuries Royal College of Surgeons of England, London, 1999

122 Holrrun S, Almqvist P, Lendahl U, Mathiesen T. Adult nestin-expressing subependymal cellsdifferentiate to astrocytes in response to brain injury. Eur J Neurosci 1997; 9: 65-75

123 Eriksson PS, Perfilieva E, Bjork-Enksson T et al. Neurogenesis in the adult humanhippocampus. Nat Med 1998; 4- 1313-7

124 Fernandez E, Palhru R, Lauretn L, Mercant D, Serra A, Calissano P Spinal cord transection inadult rats: effects of local infusion of nerve growth factor on the comcospinal tract axons.Neurosurgery 1993, 33 889-93

125 Freed CR, Breeze RE, Rosenberg NL et al. Survival of implanted fetal dopamine cells andneurologic improvement 12 to 46 months after transplantation for Parkinson's disease N EnglJ Med 1992; 327. 1549-55

126 Bakey RAE, Sladek Jr JR. Fetal nssue grafting into the central nervous system: yesterday, today,and tomorrow Neurosurgery 1993, 33: 645-7

127 Cockburn JM, Gatherer A. Facilities for rehabilitation of adults after head injury. Clm Rehab1988,2 315-8

128 Gentleman D, Gilchnst JME Follow-up of patients with severe head injury in the British Isles:current practice and the views of neurosurgeons. Eur ] Neurol 1996, 3 (Suppl 2): 52

129 Thornkll S, Teasdale GM, McEwen J, Murray GD, Roy C, Macleod D. Hospitalised headinjuries: sequelae, rehabilitation services, and outcome. / Neurotrauma 1997: 14 273

130 Brooks N, Campsie L, Symington C, Beattie A, McKinlay W. The five year outcome of severeblunt head injury: a relative's view. / Neurol Neurosurg Psychiatry 1986, 49. 764-70

131 Conzen M, Ebel H, Swart E, Skreczek W, Dette M, Oppel F. Long-term neuropsychologicaloutcome after severe head injury with good recovery. Brain Injury 1992, 6: 45-52

132 Levin HS, Gary Jr HE, Eisenberg HE et al. Neurobehavioral outcome one year after severe headinjury: experience of the Traumatic Coma Data Bank. / Neurosurg 1990; 73: 699-709

133 McAllister TW. Neuropsychiatnc sequelae of head injuries Psychiatry Clin North Am 1992;15 395-413

134 Mackay LE, Bernstein BA, Chapman PE, Morgan AS, Milazzo LS Early intervention in severehead in|ury. long term benefits of formalised program. Arch Phys Med Rehab 1992; 73:635-41

135 Pentland B, Macpherson K An attempt to measure the effectiveness of early brain injuryrehabilitation Health Bull 1994; 52 438^5

136 Schwartz ML, Sharkey PW, Anderson JA Quality assurance for patients with head injuriesadmitted to a regional trauma unit / Trauma 1991; 31: 962-7

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