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Initial Management of Head Injury - sample


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Initial Management of Head Injury provides comprehensive guidance for non-neurosurgeons on managing patients with head trauma for better patient outcomes. Targeted at emergency physicians, paramedics, general physicians, clinicians and intensivists who are part of trauma care teams, Initial Management of Head Injury gives the non-neurosurgeon all the information they need, enabling them to make accurate decisions for optimal initial care to save lives which may otherwise be lost or irretrievably impaired.

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Initial Management of Head Injury - sample

  1. 1. PART I Epidemiology 2 CHAPTER 1 Epidemiology of Acute Head Injury
  2. 2. CHAPTER 1 Epidemiology of Acute Head Injury 3 Head Injury: The Magnitude of the Problem 3 Definition of Head Injury 3 Incidence of Head Injury 3 Classification of Head Injury 4 Causative Factors 4 Changing Patterns of Head Injury 5 Organisation of Head Injury Care 7 References
  3. 3. EPIDEMIOLOGY OF ACUTE HEAD INJURY CHAPTER 1 3 Head Injury: The Magnitude of the Problem In developed and in many developing countries, trauma is the leading cause of death in the population aged under 45 years. In view of the young age of most victims, more productive years of life are lost from trauma than from cardiac and cerebrovascular disease or from cancer.1 Head injuries account for nearly half the trauma deaths. Although most trauma deaths prior to hospital admission are due to chest and multiple injuries, head injury is responsible for the majority of trauma deaths after hospital admission.2,3 Head injury is also the most common cause of permanent disability after injury and such disability may manifest even in patients with less severe degrees of head injury.4–6 Hence, head injury poses a major public health problem worldwide. It results in great personal loss and imposes a tremendous burden on health-care systems through disability and costs of care, as well as on society through the years of productive life lost. In the US, an estimated 1.5–2.0 million people experience a head injury each year; nearly 250000 of these patients require hospitalisation and approximately 52000 die. Long-term disability affects an estimated 70000–90000 people annually. The economic consequences are considerable. Lifetime medical care costs of head injuries in the US in 1985 were estimated to total US$4.5 billion, including US$3.5 billion in hospital costs alone.7–10 In low- and middle-income countries (LMIC), trauma is an increasingly important cause of death and disability. It has recently been estimated that the economic burden of trauma for 11 countries in South-East Asia is approximately US$11 billion per year.11 In these countries, large shifts of rural populations to urban areas and a rapid increase in the use of motor vehicles are outpacing efforts at injury prevention and organisation of trauma care.12,13 The multiple costs of head injury are more burdensome in these emerging economies. Definition of Head Injury Head injury may be broadly defined to include any of following:15,16 1. a documented history of a blow to the head 2. evidence of injury to the scalp in the form of swelling, abrasion or contusion 3. evidence of a fracture in a skull X-ray (or computed tomography (CT) scan) or evidence of brain injury in a CT scan performed immediately after trauma 4. clinical evidence of a fracture of the skull base 5. clinical evidence of a brain injury (loss or impairment of consciousness, amnesia, neurological deficit, seizure) The scalp,skull and brain can be injured independently and only aproportionof patientswithaheadinjurysustainaconcomitant brain injury. Conversely, a small number of patients without initial clinical evidence of an injury to the brain may develop serious complications, such as intracranial haemorrhage, brain swelling, meningitis or epilepsy. Consequently, some patients without clinical evidence of an initial injury to the brain may need evaluation at emergency departments, and even hospital admission, making a considerable impact on the health-care system.14 Incidence of Head Injury Epidemiological data are of paramount importance in planning effective preventive measures, planning and providing care for the acutely injured and rehabilitation for disabled survivors. Reliable statistics on head injury are difficult to obtain from routinely collected data from hospital admissions because of poor identification or categorisation of organ-specific injuries. In addition, estimates of the frequency of head injuries from deaths and discharges in hospital statistics do not include deaths at the site of the injury and omit patients transferred after initial assessment.13 Epidemiological factors also depend on geographic, demographic and socioeconomic factors which vary with time. In many countries, the overall incidence of head injury is difficult to determine because most statistics are derived from specific locations and minor head injuries tend to be under-reported. Hence, data from one country cannot be used as the basis for planning head injury care in another and the data from a given location need to be updated constantly. The epidemiological parameters of head injury (in adults) from diverse locations are given in Table 1.1. The mean incidence rate of hospitalised and fatal head injury for Europe is reported to be 235 per 100000 population, similar to the average rate of three reports from Australia, but much higher than that reported for the US (103 per 100000) and India (160 per 100000).17–21 The incidence of head injury, based on hospital admissions, is mostly reported from developed countries and is unlikely to apply to developing countries. Each year in the UK, 1500 per 100000 population attend an accident and emergency department with a head injury, 300 are admitted to hospital and nine die; head injury is implicated in approximately half of all trauma deaths.22 It has been estimated that for each patient admitted to hospital with a head injury, approximately three to four patients with minor head injury are seen and discharged from emergency departments.23 Classification of Head Injury Head injury can be classified as outlined below. By severity of brain injury The most commonly used modality for classifying brain injury severity is the post-resuscitation Glasgow Coma Scale (GCS).28 Traditionally, head injury has been classed by severity as mild (GCS 13–15), moderate (GCS 9–12) or severe (GCS ≤8). Based on this classification, studies of the head-injured population in high-income countries have estimated the incidence among different subsets as follows: severe head injury 5%; moderate head injury
  4. 4. 4 PART I EPIDEMIOLOGY Causative Factors In general, the main causes of head injury are road accidents, falls and assaults. However, there is considerable variation in the distribution of causes in different countries. Road accidents are responsible for the majority of head injuries in most countries.32 World Health Organization (WHO) data show that, in 2002, nearly 1.2 million people worldwide died as a result of road traffic injuries (an average of 3242 people dying each day). The type of road user accounting for most road fatalities varied in different countries: in Australia, Netherlands and the US, most were motor car users; in Malaysia and Thailand, most were motorcyclists; and in India and Sri Lanka, most were pedestrians. Between 20 million and 50 million people globally are estimated to be injured or disabled each year from traffic-related injuries. Head injury accounted for a significant proportion of such deaths and disability.33,34 Falls are an important cause of head injury,especially among young children and the elderly. Assault is a more common cause in economically depressed and densely populated inner- city areas.35 The importance of civil strife (prevalent for long periods in some areas of the world) is probably underestimated as a cause of head injury because of poor documentation. The US is unique among developed countries in that, in some locations, firearms have accounted for more head injury deaths than traffic accidents since 1990.36 Alcoholisanimportantcontributoryfactorinroadaccidents (affecting pedestrians and drivers), as well as in assaults and falls. Falls in adults related to alcohol or assault are likely to be under-reported. Changing Patterns of Head Injury In many developed countries, the trend data for road deaths from head injury have indicated a decline in recent years, attributed mainly to the implementation of preventive measures,such as seat belts,motorcycle and pedal cycle helmets, laws on alcohol limits for drivers, speed limits and improved car 5%–10%; and mild head injury 85%–90%.23,29 However, recent studies have demonstrated that patients with GCS 13 frequently have CT scan abnormalities and develop intracranial complications requiring surgical intervention, in a pattern similar to those who are considered to have moderate head injury.5,30 Hence, in this publication, mild head injury includes only patients with GCS 14 and 15 at the time of presentation at the accident and emergency department. Patients with GCS 13 are considered to have sustained moderate head injury. The use of the degree of cerebral concussion and the duration of post-traumatic amnesia to define injury severityisdiscussedinChapter4(NeurologiocalEvaluation) and Chapter 15 (Sports-Related Head Injury). International Classification of Diseases (ICD) Code31 This patho-anatomical classification is used for epidemiological purposes, as well as for hospital record keeping (see Table 1.2). Table 1.1 Comparison of selected epidemiological parameters of head injury from different locations (for adults) Europe22 US20,24,25 Australia17,19,27 East Asia (Taiwan)26 India18 Incidence per 100000 population (hospitalised patients and deaths) 235 103 226 334 160 Mortality rate per 100000 population 15.4 18.1 Not reported 38 20 Severity (% mild/moderate/severe) 79/12/9 80/10/10 76/12/11 78/9/13 71/15/13 External cause (% fall/MVA/violence) 37/40/7 21/25/6 49/25/9 23/65/7 59/25/14 MVA, motor vehicle accident. Table 1.2 International Classification of Diseases (ICD-10)31 Injuries to the Head (S00–S09) S 0-0 Superficial injury of the head S 0-1 Open wound of the head S 0-2 Fractures of skull and facial bones S 0-3 Injuries of joints and ligaments of the head S 0-4 Injury of cranial nerves S 0-5 Injury of the eye and orbit S 0-6 Intracranial injury S 0-7 Crush injury of the head S 0-8 Traumatic amputation of part of head S 0-9 Other and unspecified injury of head Sub categorisation of S 0-6: Intracranial injury S 06-0 Concussion S 06-1 Traumatic cerebral oedema S 06-2 Diffuse brain injury S 06-3 Focal brain injury S 06-4 Epidural haemorrhage S 06-5 Traumatic subdural haemorrhage S 06-6 Traumatic subarachnoid haemorrhage S 06-7 Intracranial injury with prolonged coma S 06-8 Other intracranial injuries S 06-9 Intracranial injury unspecified
  5. 5. EPIDEMIOLOGY OF ACUTE HEAD INJURY CHAPTER 1 5 and road design.8,32 In the US, an analysis of national mortality trends indicated a 22% decline in rates of death associated with head injury from 1979 to 1992, attributed largely to injury prevention and improved treatment.8 However, rates for road deaths may be much higher and rising in LMIC, where such measures have not yet been implemented and where there has been a marked increase in vehicular traffic as a result of rapid economic growth.37 In many developed countries, there has been an increase in the incidence of head injury caused by falls, especially in the increasing elderly population. A recent study from Sweden reported that falls were the most common cause of head injury (58%), followed by traffic accidents (16%) and persons hit by objects (15%).38 In some parts of the US, the beneficial effect of a decline in motor vehicle-related head injury was undermined by a marked increase in firearm-related head injury.8,34,39 Violence is unfortunately increasing in prominence as a cause of childhood injury, especially in economically impoverished areas and in areas of civil strife.40 Organisation of Head Injury Care (Table 1.3) Mortality and morbidity can be significantly reduced by (i) preventive strategies that reduce the number and severity of head injuries; and (ii) head injury care systems that aim to minimise damage to the brain after an injury by optimising: 1. prehospital care and triage 2. initial management at emergency departments 3. urgent evacuation of significant intracranial haematomas 4. high-quality neurointensive care 5. rehabilitation Instituting these strategies requires reliable data on the incidence, causation, distribution and degrees of severity of head injuries in different locations in a country or region under consideration. Auditing the efficacy of a head injury care system may identify preventable lapses in management and is important in the planning and improvement of care. In an audit of a state trauma service in the state of Victoria, Australia (published in 2000), the following lapses were identified.45 Prehospital phase An inability to intubate, prolonged accident scene time and no intravenous access. In the emergency room Inappropriate reception, delay in arrival of a consultant, lack of neurosurgical consultation, failuretoperformacranialCTscan,inadequatebloodgases and oxygen monitoring, inadequate fluid resuscitation, delayed respiratory resuscitation and delayed despatch to the operating room. In the operating room Failure to institute intracranial pressure(ICP)monitoring,inadequatefluidadministration and inappropriate anaesthetic technique. Table 1.3 Organisation of a head injury care system33,41–44 Preventive measures Public awareness programmes that target: The behaviour of drivers and pedestrians Workplace accidents (e.g. construction sites, factories) Accidental injury at home (especially in children) Legislative measures Alcohol control (basal alcohol concentration <100µg/dL in most countries) Speed limits Use of safety devices (seat belts, airbags, restraints for infants; helmets for motor cyclists, cyclists, construction workers) Improved infrastructure Road design, warning devices, speed limits Improved safety in vehicles Seatbelts, air bags, infant restraints Side impact protection Firearm registration (to reduce the general availability of firearms) • • • • • • • • •
  6. 6. Advanced trauma systems developed in developed countries depend on teamwork involving multiple specialties, proper sequence and timing of interventions and adequate supporting equipment, resources and personnel. Such systems may not be easily adapted to LMIC.51,52 Therefore, a head injury care system in a given locality must take into account the local conditions, as well as financial and manpower resources. A study in Latin America showed that prehospital trauma care can be improved significantly by instituting simple, low-cost measures such as Prehospital Basic Trauma Life Support training for emergency medical personnel, increasing sites of dispatch of emergency medical personnel, use of oropharyngeal airways, suction, administration of oxygen, intravenous fluid resuscitation and cervical collar immobilisation. Implementation of such measures nearly halved the deaths en route, did not increase mean time spent at the accident site and increased costs only minimally.53 In LMIC with limited health care resources, the institution of preventive measures, organisation of prehospital care, triage and optimal initial management in emergency departments will have a substantial impact on the outcome of trauma.33 6 PART I EPIDEMIOLOGY In the intensive care unit Failure to institute ICP monitoring. Although programmes that provide optimal care for head injuries of all degrees of severity will reduce mortality and morbidity, the most profound impact of such programmes has been the improved management of moderate and mild head injuries.46,47 Mild injuries are much more common and yet some patients with mild injury develop life-threatening, but remediable, complications. Appropriate triage of these patients is extremely important, particularly when CT scanning and neurosurgical expertise are scarce. The publication of practice guidelines for head injury care (such as those of the Brain Trauma Foundation43 , the Neurosurgical Society of Australasia48 and the European Brain Injury Consortium49 ) has been very useful in standardising head injury management. However, a recent study in the US revealed that only 16% of the trauma centres surveyed were in full compliance with the guidelines of the Brain Trauma Foundation.50 Table 1.3 (cont) Organisation of a trauma-care system Patient retrieval by a well-designed EMS, with adequately trained EMS personnel, a well-equipped ambulance service acting in coordination with police and other emergency services; the EMS should provide: Immediate basic resuscitation at the scene of an accident Proper triage of the injured Rapid and safe transfer to an appropriate institution as determined by the nature and severity of the injury A streamlined referral system based on available resources at trauma care institutions in the region and their proximity A three-level organisation of trauma care institutions: Level 3 centres (rural hospitals), with basic care facilities, provide initial resuscitation and safe transfer Level 2 centres (community trauma centre, district hospital), with a well-designed emergency department with ATLS- trained staff, emergency operating theatre facilities, the services of a General Surgeon, an Orthopaedic Surgeon, an Anaesthetist and, optimally, a CT scan facility and, in some level 2 centres, the services of a Neurosurgeon, provide initial care of head injury if a Neurosurgeon is available on-site or, if a Neurosurgeon is not available, immediate management of life-threatening extracranial injury, initial resuscitation and evaluation of patients with head injury (those patients requiring neurosurgical care are transferred to a level 1 centre) Level 1 centres (regional trauma centres, teaching hospital), with, in addition to facilities available at a level 2 centre, 24 hour availability of CT scanning, a 24 hour neurosurgical service with an operating theatre for emergency neurosurgery, a well-equipped Neurosurgical Intensive Care Unit, observation wards, facilities for head injury rehabilitation, educational and research programmes, provide comprehensive management of all aspects of head injury • • • • • • EMS, emergency medical service; ATLS, advanced trauma life support.
  7. 7. EPIDEMIOLOGY OF ACUTE HEAD INJURY CHAPTER 1 7 References 1. Rockett IRH, Smith GS. Injury related to chronic disease: international review of premature mortality. Am J Public Health 1987;77:1345–7. 2. Daly K, Thomas P. Trauma deaths in the south west Thames region. Injury 1992;23:393–6. 3. Demetriades D, Murray J, Charalambides K, et al. Trauma fatalities: time and location of hospital deaths. J Am Coll Surg 2004;198:20–6. 4. Kraus JF. Epidemiology of head injury. In: Cooper PR, ed. Head Injury, 3rd edn. Baltimore: William Wilkins, 1993:1–25. 5. Shackford SR, Mackersie RC, Holbrook TL, et al. The epidemiology of traumatic death: a population-based analysis. Arch Surg 1993;128:571–5. 6. Masson F, Thicoipe M, Aye P, et al. Epidemiology of severe brain injuries: a prospective population-based study. J Trauma Infect Crit Care 2001;51(3):481–9. 7. Max W, Mackenzie EJ, Rice DP. Head injuries: costs and consequences. J Head Trauma Rehabil 1991;6:76–91. 8. Sosin DM, Sniezek JE, Waxweller RJ. Trends in death associated with traumatic brain injury, 1979 through 1992: success and failure. JAMA 1995;273:1778–80. 9. Sosin DM, Sniezek JE, Thurman DJ. Incidence of mild and moderate brain injury in the United States, 1991. Brain Inj 1996;10:47–54. 10. Thurman D, Guerrero J. Trends in hospitalization associated with traumatic brain injury. JAMA 1999;282:954–7. 11. Asian Development Bank. Report of Asian Development Bank, 2002. Manila: Asian Development Bank, 2003, 12. Murray CJL, Lopez AD. Mortality by cause for the eight regions of the world: global burden of disease study. Lancet 1997;349:1269–76. 13. Sethi D, Zwi AB. Traffic accidents: another disaster? Eur J Public Health 1999;9:65–7. 14. Jennett B. Epidemiology of head injury. Arch Dis Child 1998;78:403–6. 15. Brookes M, Macmillan R, Cully S, et al. Head injuries in accident and emergency departments. How different are children from adults. J Epidemiol Community Health 1990;44:147–51. 16. Jennett B, Macmillan R. Epidemiology of head injury. BMJ 1981;282:101–4. 17. Badcock K. Head injury in South Australia: incidence of hospital attendance and disability based on a one-year sample. Community Health Studies 1998;XII:428–36. 18. Gururaj G, Sastry Koeluri V, et al. Neurotrauma Registry in the NIMHANS. Bangalore: National Institute of Mental Health and Neurosciences, 2004. 19. Hillier S, Hiller J, Metzer J. Epidemiology of traumatic brain injury in South Australia. Brain Inj 1997;11:649–59. 20. Langlois J, Rutland-Brown W, Thomas K. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Atlanta: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, 2004. 21. Tagliaferri F, Compagnone C, Korsic M, et al. A systematic review of brain injury epidemiology in Europe. Acta Neurochir (Wien) 2006;148(3):255–68. 22. Hutchinson PJ. Future perspectives in the acute management of head injury. Br J Surg 2003;90:769–71. 23. Miller JD. Head injury. J Neurol Neurosurg Psychiatry 199356:440–7. 24. Torner J, Choi S, Barnes T. Epidemiology of head injuries. In: Marion D, ed. Traumatic Brain Injury. New York: Thieme, 1999:9–28. 25. Kraus J, McArthur D. Brain and spinal cord injury. In: Nelson M, Tanner C, eds. Neuroepidemiology: from principles to practise. New York: Oxford University Press, 2004:1291–306. 26. Chiu W, Yeh K, Li Y, Gan Y, et al. Traumatic brain injury registry in Taiwan. Neurol Res 1997;19:262–4. 27. Tate R, McDonald S, Lulham J. Incidence of hospital-treated traumatic brain injury in an Australian community. Aust NZ J Public Health 1998;22:419–23. 28. Jennett B, Teasdale GM. Assessment of coma and impaired consciousness: a practical scale. Lancet 1974;ii:81–4. 29. Ruff RM, Marshall LF, Crouch J, et al. Predictors of outcome following severe head trauma: follow-up data from the Traumatic Coma Data Bank. Brain Inj 1993;7(2):101–11. 30. Stein SC, Ross SE. Minor head injury: a proposed strategy for emergency management. Ann Emerg Med 1993;22:1193–6. 31. World Health Organization. The International Statistical Classification of Diseases and Health Related Problems, ICD-10, 2nd edn. Geneva: WHO, 2005. 32. Jennett B. Epidemiology of head injury. J Neurol Neurosurg Psychiatry 1996;60:362–9. 33. Report of the Injury Control Unit. Kuala Lumpur: Ministry of Health, Malaysia, 1996. 34. World Health Organization. World Report on Traffic Injury Prevention, 2004. Geneva: World Health Organization, 2004, http://www.who. int/world-healthday/./infomaterials/world_ report 35. Cooper KD, Tabbador K, Hauser WA, Shulman K, Feiner C, Factor PR. The epidemiology of head injury in the Bronx. Neuroepidemiology 1983;2:70–88. 36. Langlois JA, Rutland-Brown W, Thmoas JE. Traumatic brain injuries in the United States: emergency deparment visits, hospitalizations and deaths. Atlanta: National Centre for Injury Prevention & Control, 2006, http://www. TBI%20in%20the%20US_Jan_2006.pdf 37. Hung C, Chiu W, Tsai C, et al. Epidemiology of head injury in Hualien County, Taiwan. J Formos Med Assoc 1991;262:1227–33. 38. Andersson EH, Bjorklund R, Emanuelson I, et al. Epidemiology of traumatic brain injury: a population based study in western Sweden. Acta Neurol Scand 2003;107:256–9. 39. Masson F, Vecsey J, Salmi LR, et al. Disability and handicap 5 years after a head injury: a population-based study. J Clin Epidemiol 1997;50:595–601. 40. Meyer AA. Death and disability from injury: a global challenge. J Trauma 1998;44:1–12. 41. American College of Surgeons Committee on Trauma. Resources for optimal care of the injured patient. Chicago: American College of Surgeons, 1999. 42. Fearnside MR, Simpson DA. Epidemiology. In: Reilly P, ed. Head Injury. London: Chapman & Hall, 1997:1–23. 43. Bullock RM, Chesnut RM, Clifton GL, et al. Guidelines for the management of severe head injury. J Neurotrauma 2000;17:449–627. 44. Sampalis JS, Lavoie A, Boukas S, et al. Trauma center designation: initial impact on trauma- related mortality. J Trauma Injury Infect Crit Care 1995;39:232–9. 45. Rosenfeld JV, McDermott FT, Laidlaw JD, et al. The preventability of death in road traffic fatalities with head injury in Victoria, Australia. J Clin Neurosci 2000;7:507–14. 46. Klauber MR, Marshall LF, Luerssen TG, Frankowski R, Tabaddor K, Eisenberg HM. Determinants of head injury mortality: importance of the low risk patient. Neurosurgery 1989;24:31–6. 47. Maas AIR, Dearden M, Servadei F, et al. Current recommendations for neurotrauma. Curr Opin Crit Care 2000;6:281–92. 48. The Royal Australian College of Surgeons. Guidelines for the Management of Acute Neurotrauma in Rural and Remote Locations. Melbourne: The Royal Australian College of Surgeons, 2000, au/documents/Neurotrauma.pdf 49. Maas AIR, Dearden NM, Teasdale GM, et al. EBIC-Guidelines for management of severe head injury in adults. Acta Neurochir (Wien) 1997;139:286–94. 50. Hesdorffer DC, Ghajar J. Predictors of compliance with the evidence-based guidelines for traumatic brain injury care. A survey of United States trauma centers. J Trauma Injury Infect Crit Care 2002;52:1202–9. 51. Sethi D, Aljunid S, Saperi SB, et al. Injury care in low and middle income countries: identifying potential for change. Inj Control Safety Promotion 2000;7:153–67. 52. Kirsch TD. Emergency medicine around the world. Ann Emerg Med 1998;32:237–8. 53. Arreola-Risa C, Mock CN, Lojero-Wheatly L, et al. Low-cost improvements in prehospital trauma care in a Latin American city. J Trauma 2000;48(1):119–24.
  8. 8. PART II Basic Principles 10 CHAPTER 2 Pathophysiology of Acute Non-Missile Head Injury 33 CHAPTER 3 Intracranial Pressure
  9. 9. CHAPTER 2 Pathophysiology of Acute Non-Missile Head Injury 11 Introduction 11 Phases of Acute Head Injury 11 Biomechanics of Head Injury 11 Impact Injury 13 Inertial Injury 14 Diffuse Axonal Injury 14 Cranial Injury by Static Loading 14 Primary Brain Injury 14 Focal Injuries 16 Diffuse Brain Damage 18 Evolution of Primary Brain Injury 18 Damage to Parenchymal Cells 19 Damage to the Cerebral Vasculature 21 Secondary Brain Injury 21 Traumatic Intracranial Haematomas 25 Post-traumatic Brain Swelling 26 Focal Brain Damage Secondary to Brain Shifts and Herniations 26 Secondary Brain Insults 26 Secondary Insults due to Extracranial Causes 27 Ischaemic Brain Damage Following Acute Head Injury 28 Mechanisms Contributing to Repair of Damage from the Initial Injury 28 Role of Genetic Profile in Determining the Outcome of Head Injury 29 Summary 30 References
  10. 10. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 11 INTRODUCTION The pathophysiological changes following acute head injury are complex. The injury may be caused by different mechanisms, often in combination. Changes following injury occur at the molecular, biochemical, cellular and macroscopic levels. They are dynamic and may be adversely influenced by events occuring after the initial injury. Phases of Acute Head Injury Acute head injury is a progressive process. The initial, or primary, injury is caused by the mechanical deformation of brain tissue and blood vessels at the moment of injury. At a macroscopic level, there may be gross disruption of brain tissue; at a microscopic level, there may be damage to the brain parenchymal cells (neurones, axons, glial cells) and the microcirculation (arterioles, capillaries and venules). The primary injury may evolve over hours or days through a series of inter-related biochemical and metabolic changes, inflammatory reactions and progressive structural damage to neurones, glia and the cerebral vasculature. The consequences of these dynamic changes include cellular swelling, cell death by necrosis and apoptosis, intracranial haemorrhage, brain swelling, raised intracranial pressure and cerebral ischaemia. Hence, the pathophysiological changes in acute head injury can be considered at three levels (Fig. 2.1). Secondary injury refers to the delayed effects of events initiated by the injury. The term may be applied to the evolving deleterious effects of the primary injury referred to above but in clinical terms secondary injury is generally applied to the effects of post-traumatic intracranial haematomas, brain swelling and increased intracranial pressure and, in the later stages, to hydrocephalus and infection. Secondary brain insults are systemic events occurring after injury that have the potential to add to the damage to neurones, axons and the cerebral vasculature, already rendered susceptible by the primary injury. The principal secondary insults are hypoxia, hypotension, hypercarbia , hyperpyrexia and electrolyte imbalances. There is increasing evidence that the primary injury stimulates reparative processes. Therefore, the magnitude of any head injury is determined by the total effects of the primary and secondary brain injury, as well as secondary brain insults, and may be modified by reparative processes (Fig. 2.2).1 Biomechanics of Head Injury The effects that an injury has on the brain and its coverings tissues may be analysed in terms of the forces applied. Impact loading refers to the direct effects that contact has on the head; for example, when the moving head strikes an object and is prevented from moving after impact. Impact loading results primarily in injuries at the site of impact. Inertial loading refers to the effects of acceleration or deceleration on the brain; for example, when a pedestrian is struck on the body by a moving vehicle and the head is set in sudden motion or in a high-speed motor vehicle collision, when the body of the driver is stopped by the steering wheel and the head continues to decelerate. The pattern of brain injury is affected by the subsequent motion within the cranium. This is invariably a combination of linear (translational) motion and angular motion. Most injuries are caused by a combination of impact and inertial forces. Biomechnical analysis has lead to a greater understanding of the effects of different types of impact and, hence, to advances in methods of protecting the brain. For clinical purposes, it is useful to consider injury in terms of focal and diffuse components. Impact Injury A direct impact to the cranium results in local distortion and propagation of stress waves from the area of impact through successively deeper layers of the cranium (i.e. scalp–skull– meninges–brain parenchyma), the degree of distortion of the tissue and the depth of propagation of the stress waves being determined by the velocity of impact. Impact injury usually involves energy of a high magnitude acting directly on the skull for a short duration (approximately <50 msec).1 Cascades of cellular, biochemical, metabolic, inflammatory changes, immunological reactions Ischaemic changes, cellular swelling, cell death (necrosis and apoptosis) Macroscopic changes (focal or diffuse damage) Contusions, haematoma, brain swelling, brain shifts and herniations Microscopic changes Neurones, glia Axonal injury Changes in the microcirculation Capillary damage, hypoperfusion, oedema, hyperaemia, haemorrhage, ischaemia ▲ Figure 2.1 Spectrum of the pathophysiological changes after acute head injury
  11. 11. 12 PART II BASIC PRINCIPLES ▲ Figure 2.2 Overlapping phases of head injury ▲ Figure 2.3 Effects of direct impact injury from a blunt object with a restricted area of impact. Fragments of bone separate from the rest of the cranium and are driven below the level of the surrounding bone, resulting in a depressed fracture (black arrow). The underlying dura may become lacerated and the underlying brain may be damaged, resulting in a focal contusion (open arrows). Depending on the characteristics of the injury, such as the energy of impact and the nature of the impacting surface, several patterns of damage may result, as described below. Scalp haematoma The dermal and subcutaneous layers can distribute the force of an impact and reduce its effects up to a point without structural damage. However, when the force exceeds the capacity of the scalp to dissipate the energy, a scalp haematoma or a scalp laceration will result. Linear skull fracture When the skull is impacted over a large area, skull deformation may result, with inward and outward bending. With a moderate force of impact, or if the skull is more resilient, as in an infant, inward and outward bending of the skull may occur without fracture. However, significant inbending of the more mature, rigid skull will result in a linear fracture. Impact forces can propagate stress waves through the surrounding bone and result in a skull fracture remote from the impact site. Thus, fractures in the base of the skull may result from an impact to the skull vault.2 Depressed fracture When the impacting force is distributed over a relatively small area, such as from a blow by a hammer, a fragment or fragments of bone may separate from the cranium and are driven inwards to a depth equivalent to or more than the thickness of the skull, resulting in a depressed fracture. The underlying dura may either remain intact or be lacerated. The underlying brain may be contused (Fig. 2.3). Penetrating injury High-energy impact from an object with a very small surface area (especially a sharp, pointed object) may lead to deep penetration of the cranium through very narrow rents in the scalp and cranial bone, as well as penetration of the dura, and may result in a cerebral contusion or intracerebral haematoma (Fig. 2.4). Extradural haematoma The inward and outward bending of the skull can strip the dura from its attachment to the inner table of the skull, creating a potential space. If the dural separation or an overlying skull fracture damages a meningeal vessel (most commonly the middle meningeal artery, but also meningeal veins or dural sinuses), an extradural haematoma (EDH) can result (Fig. 2.5). ▲ Figure 2.4 Impact from a sharp, pointed object resulting in a penetrating injury. Deep penetration can occur through a very narrow rent in the cranial bone, resulting in penetration of the dura and small fragments of bone being driven into the underlying brain with contusion of the underlying brain (black arrow). An intracerebral haematoma may also result (white arrowheads).
  12. 12. Inertial Injury Contre coup contusions See Fig. 2.6a–d. A direct impact can result in movement of the skull and the brain in a direction away from the impacting force. The brain lags behind the skull because of its inertia, and because it is surrounded by cerebrospinal fluid (CSF), and then continues to move once the skull has stopped. During such differential movement, the brain can be damaged at points remote from the impact (e.g. by the irregular surfaces of the floor of the anterior and middle cranial fossae and the lesser wing of the sphenoid),resulting in contre coup contusions,typically located in the frontal and temporal poles and the orbital surfaces of the frontal lobes (Fig. 2.6a–d). Contre coup contusions may also occur in the lateral and inferior surfaces of the temporal lobes, as well as in the cortex above and below the Sylvian fissure.7 Another mechanism for contre coup injury may be the effect of relative movement between the skull and the brain, leading to pressure changes in the brain parenchyma, typically at the poles of the brain (especially in the frontal and temporal poles). Negative pressure is created at the onset of movement, when the brain lags behind the skull, and positive pressure is created when the still-moving brain impacts the stationary skull. When such pressure change strains exceed the tolerance of the brain parenchyma and vasculature, contre coup contusions and ICH can result. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 13 ▲ Figure 2.5 Direct impact injury leading to an extradural haematoma (EDH). Direct impact can result in a sub-galeal haematoma in the scalp (black arrow). The inward and outward bending of the skull can result in a skull fracture, which is usually located directly beneath the scalp haematoma. The dura may become stripped from the inner table of the skull and an EDH (open arrow) results from a tear in a meningeal vessel. ▲ Figure 2.6 Contre coup contusions after a direct impact injury. (a) An impact to the occipital region results in differential movement between the brain and the rough, irregular surfaces of the floor of the anterior cranial fossa and the temporal fossa (open arrows). (b) Such motion can lead to cerebral contusions involving the inferior surfaces of the frontal lobes and the temporal poles (black arrowheads). (c, d) Computed tomography scans showing an area of impact over the right parieto-occipital region (white arrow) leading to contre coup contusions in the frontal lobes (white arrowheads). d c a b
  13. 13. 14 PART II BASIC PRINCIPLES ▲ Figure 2.8 Effects of compression. Forces of compression can lead to significant deformation of the skull and extensive comminuted fractures of the skull vault (black arrowheads) that may extend to the skull base (curved arrows). Primary Brain Injury Focal Injuries CEREBRAL CONTUSIONS Contusionsmayresultfromfocalimpactordiffuseacceleration– deceleration forces. Stress waves propagating from the area of impactmaydeformbraintissuedirectlyunderneath.Whensuch strains exceed the tolerance of brain tissue and its vasculature, there is a disruption of the brain tissue and vasculature that results in a direct cerebral contusion (coup contusion; i.e. a contusion directly beneath the site of impact. This is seen most clearly in contusions that develop beneath a fracture Fig. 2.9 (‘fracture contusions’). Contusions may also be associated with diffuse injury and are most commonly located in the frontal pole, orbital surface of the frontal lobe, the temporal pole and inferior and lateral surfaces of the temporal lobe. Contusions are often multiple and may be associated with other lesions, such as acute SDH, EDH and diffuse axonal injury (DAI). A contusion may be localised to the cerebral cortex or may extend deeper to involve the underlying white matter (Fig. 2.10a). Contusional damage may also extend over the surface of the cerebral cortex and there may be associated subarachnoid haemorrhage (SAH). The severity of a contusional injury may be judged by the surface extent and depth, as well as whether the damage is solitary or multiple.4 The damage to the vasculature principally involves capillaries. Disruption of larger blood vessels at a site of impact can result in an acute SDH (termed ‘complicated SDH’) or an ICH (Fig. 2.9). A typical cerebral contusion consists of a central area of haemorrhageadmixedwithareasof non-haemorrhagicnecrosis and partly damaged,oedematous brain (Fig 2.10a).With time,this central area becomes surrounded by a zone of pericontusional Acute SDH Acute SDH can result from the tearing of veins that bridge the brain and venous sinuses or the dura (uncomplicated acute SDH). Less commonly, an acute SDH can result from the rupture of a cortical artery (Fig. 2.7a, b). Diffuse Axonal Injury (discussed later) ▲ Figure 2.7 Relative movement between the skull and the brain can result in the tearing of veins that bridge the brain and venous sinuses or, less often, cortical arteries (inset, curved arrows), resulting in acute subdural haematoma. Cranial Injury by Static Loading This uncommon injury occurs when compressive forces are exerted on the stationary head (e.g. a wheel of a vehicle or a heavy weight compressing the head against the floor). Such forces occur over a longer duration (>200 msec) compared with impact forces and usually lead to significant deformation of the skull, extensive comminution of the skull vault and fractures of the skull base (Fig. 2.8). The degree of brain injury and the risk of development of an extra-axial haematoma depend on the force. Because there is no diffuse injury, consciousness may be preserved, even in the presence of extensive injury to the cranium.3
  14. 14. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 15 ▲ Figure 2.10 Cerebral contusion. (a) A computed tomography (CT) scan demonstrating typical features in a cerebral contusion: location at the cortical surface and involvement of the grey matter at the crests of the gyri. There is a central area of haemorrhage (white arrow) admixed with areas of low density (black arrow) representing non-haemorrhagic necrosis or partly damaged, oedematous brain and a zone of pericontusional oedema (white arrowhead). (b) A CT scan performed within the first 24 hours after a head injury, showing a small contusion (black arrow) in the basal portion of the left frontal lobe. (c) A repeat CT scan performed 72 hours later showing a marked increase in the size of the contusion due to an increase in the haemorrhagic component (black arrow), as well as an increase in the surrounding oedema (white arrowhead). b c a ▲ Figure 2.9 Effects of direct impact injury from a blunt object, with a broad area of impact. (a, b) The inward and outward bending of the skull can lead to a linear fracture. The (a) compressive (small black arrows) and (b) tensile (small open arrows) strains created can damage the brain parenchyma and its vasculature, resulting in (c) a direct cerebral contusion (white arrowheads) and a contusion-related acute subdural haematoma (large black arrow). (d) Computed tomography (CT) scan showing a cerebral contusion underneath a comminuted fracture (white arrows). a b c d
  15. 15. 16 PART II BASIC PRINCIPLES Herniation contusions occur when the medial parts of the temporal lobe impinge on the free edge of the tentorium or the cerebellar tonsils make contact with the foramen magnum at the time of injury. Gliding contusions are haemorrhagic lesions in the cerebral cortex and subjacent white matter that typically result from shearing injuries and are now considered to be part of the vascular damage associated with diffuse injuries.2 CEREBRAL LACERATIONS Cerebral lacerations resemble contusions, except that the pia- arachnoid on the surface of the involved area in the cerebral cortex is disrupted. Lacerations of the frontal and temporal lobes are usually associated with other lesions, such as ICH and acute SDH. This combination is termed a ‘burst’ frontal or temporal lobe and the SDH is termed a ‘complicated SDH’.1 Cerebral lacerations may also result from a penetrating injury of the cranium and depressed skull fractures when the sharp edges of the in-driven bone may disrupt the underlying cortex and the pia-arachnoid covering. Diffuse Brain Damage The most important cause of diffuse brain damage is shearing force, which affects all components of the brain, in particular axons and the cerebral vasculature.2,18 Minor strains cause transient stretching of the axons and cerebral vasculature. The typical clinical manifestation of minor diffuse injury is a momentary loss of consciousness followed by recovery. Axons subjected to severe strain may undergo immediate disruption, this process being termed primary axotomy. However, most axons subjected to shearing strain do not undergo immediate disruption. Some may undergo progressive swelling followed by secondary axotomy from 4 hours to several days after injury. Others, less severally injured, may be able to repair the cytoskeletal damage.19–21 Axonal injury may be focal or widely distributed in the white matter of the cerebral hemispheres (diffuse axonal injury) (Fig. 2.11). Severe shearing strain also leads to diffuse vascular injury. Diffuse brain injury is often associated with ischaemic/ hypoxic injury and brain swelling. DIFFUSE AXONAL INJURY In mild forms of DAI, microscopic foci of axonal damage are typically distributed in the white matter of the parasagittal cortex and the corpus callosum. However, with increasing severity of injury (increased velocity of injury), such foci are also demonstrated in the internal capsule, the thalami, the cerebellum and in the ascending and descending tracts of the brain stem1,3,19,22 (Fig. 2.11a, b). In the more severe forms of DAI, areas of axonal damage may be sufficiently large to be visible on magnetic resonance imaging (MRI) as non-haemorrhagic lesions.23 Adams et al.24 proposed of a grading system for DAI. In Grade 1 DAI, abnormalities are limited to histological evidence of axonal damage throughout the white matter without focal concentration in either the corpus callosum or in the brain stem. oedema.Insomeinstances,atraumaticICHmaydevelopwithin a cerebral contusion. Blood flow is characteristically absent in the central core of the contusion and is reduced in the zone of pericontusional oedema, where autoregulation is impaired (vasoparalysis). Therefore, the zone of partially damaged cells at the periphery of a contusion is vulnerable to any further reductions in perfusion by a reduction in mean arterial pressure, increased intracranial pressure or vasoconstriction following hypocapnia as a result of hyperventilation.5,6 EVOLVING CHANGES IN CONTUSIONS A contusion may increase progressively in size, beginning hours after the injury (Fig. 2.10b, c). This may occur as a result of increased bleeding and/or swelling, as outlined below. Enlargement of the haemorrhagic component The haemorrhagic component of the contusion can enlarge by coalescenceof smallhaemorrhagesordelayedhaemorrhage secondary to vascular damage. Yamaki et al. demonstrated that the haemorrhagic component of cerebral contusions reaches a maximum 12 hours after the injury in 84% of patients, although some patients may be at risk of delayed haemorrhage for a longer period.8 Kaufmann assessed the risk of delayed haemorrhage within a contusion to be maximal in the first 3–4 days after injury.9 Coagulopathy associated with injury to the brain parenchyma may contribute to the risk of delayed haemorrhage.9 A high incidence of bleeding into the contusions has been reported to occur in alcoholic patients and patients on anticoagulant therapy.10 Increased swelling of the central core of the contusion as well as in the pericontusional zone Partially damaged brain parenchymal cells in the core, as well as in the pericontusional zone, may swell (cytotoxic oedema). In the necrotic areas of the contusion, macromolecules are degraded into smaller molecules, leading to an increase in tissue osmolarity, drawing water from the intravascular compartment into areas of contusion necrosis (osmolar oedema).11 Swelling in the central area of a contusion may lead to compression of the pericontusional zone, resulting in further ischaemia and swelling. Swelling in the pericontusional area may reach a maximum around 48–72 hours after injury.8,12 The mass effect of cerebral contusions from delayed haemorrhage and swelling usually peaks around 3–5 days (although it may range from 24–48 hours to 7–10 days, even, rarely, up to 3 weeks after an injury).13,14 Usually after the first week there is a slow reduction in the volume of the contusion owing to a reduction in swelling, liquefaction and resorption of the haemorrhagic component. Even small contusions that initially appear relatively innocuous have the potential to enlarge and cause increased intracranial pressure. Sudden and catastrophic deterioration may occur in patients who initially appeared relatively neurologically intact (the ‘talk and die’ or ‘talk and deteriorate’ category).15 Contusions in the temporal fossa and those involving both frontal lobes are most likely to lead to such deterioration.16,17
  16. 16. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 17 is related to the level of consciousness immediately after the injury, the duration of the post-traumatic unconscious state and the outcome from head injury. Patients who sustain severe DAI may succumb in the early stages after injury or survive with severe impairment. Concussion is a clinical term that implies immediate but transient impairment of the conscious state after a head injury, followed by complete recovery of consciousness. Magnetic resonance imaging and post-mortem pathological studies have found evidence of axonal injury in deep white matter tracts and in the brain stem in patients who had made an apparently complete recovery from concussion.18,23 These lesions may be the basis for persistent symptoms and neuropsychological sequelae in some patients after a typical concussional injury. In a patient who recovers from concussion without any sequelae, the disturbance of axonal function may have been transient or the degree of permanent injury too small to detect.14 Clinical grading of concussion is discussed in Chapter 18. DIFFUSE VASCULAR INJURY The cerebral blood vessels are more resistant to shearing strain than axons. The effects of damage to the cerebral microvasculature has already been described. Severe forms of diffuse vascular injury may be evident as multiple petechial haemorrhages and are often found in patients who die within minutes of a closed head injury.25 Tissue tear haemorrhages associated with DAI that are small (<2 cm in diameter), discrete and located in typical sites (corticomedullary junction, deep white matter, basal ganglia and posterolateral midbrain) are also a form of diffuse vascular injury. Grade 2 DAI is defined by a wider distribution of axonal injury accompanying a larger focus of axonal damage in the corpus callosum, whereas Grade 3 DAI is characterised by diffuse damage to axons associated with larger foci of axonal damage in both the corpus callosum and brain stem. Haemorrhage may occur in the larger foci of axonal damage in the corpus callosum and brainstem as a result of diffuse vascular damage (Fig. 2.11c).24 Diffuse axonal injury disrupts the neuronal interconnections between the cerebral cortex and the brain stem reticular formation. Disruption of these interconnections contributes to impairment or loss of consciousness in patients who sustain head injury. With progressively severe injury, the extent and depth of axonal injury increases.18 Hence, the severity of DAI a b ▲ Figure 2.11 Diffuse axonal injury. (a) Shearing forces in the brain (curved arrows) created by angular motion. (b) Foci of microscopic diffuse axonal injury distributed throughout the parasagittal white matter in the cerebral hemispheres (open arrows), in the corpus callosum, typically in the splenium (black arrow), and in the dorsolateral aspect of the midbrain (black arrowhead). (c) Computed tomography scan showing a haemorrhagic focus of axonal damage (a ‘marker’ lesion) in the deep white matter (white arrow). c
  17. 17. Evolution of Primary Brain Injury Damage to Parenchymal Cells The forces associated with the primary injury may immediately and irreversibly destroy some neurones, axons and glial cells. In partially damaged cells and axons, complex biochemical and metabolic events are initiated, which may lead to cellular swelling and delayed cell death over a period of minutes to days.21 These events initiated by mechanical deformation are extremely complex and incompletely understood. They include the following. Excitotoxiccascade Inthisscenario,mechanicaldeformation of the neuronal cell membrane results in depolarisation, major ionic fluxes and the release of excitatory amino acids, such as glutamate. There is an efflux of intracellular potassium and an influx of extracellular sodium and calcium. The entry of sodium and calcium is accompanied by water. The excess potassium in the extracellular space is takenupbyastrocytes,whichswell.21,26 Theinfluxofcalcium into the neurone activates enzymes, including calpains, which destroy the internal architecture (cytoskeleton) of the cell, interfere with mitochondrial energy production and trigger the release of free radicals. Free radicals initiate cell membrane lipid peroxidation, further disruption of ionic permeability, further cellular swelling and, finally, cell death through both necrotic and apoptotic processes (Fig. 2.12).21,26 Inflammatory cell responses Trauma-induced cytokine release and leucocyte accumulation in the injured brain 18 PART II BASIC PRINCIPLES Initial injury Release of excitatory amino acid neurotransmitters (glutamate, aspartate) Injury induced cell membrane depolarisation Opening of gated ion channels Increased influx of calcium into the cell Increased influx of sodium chloride and water into the cell Efflux of intracellular potassium into the extracellular space Activation of proteases (calpains), lipases Destruction of cellular cytoskeleton Delayed cell deathCellular swelling (cytotoxic oedema) Swelling of glial cells, extrinsic compression of capillaries, ischaemia ▲ Figure 2.12 Excitotoxic cascade. The sequence of deleterious events in brain parenchymal cells, triggered by the excitotoxic cascade and their consequences.21,26,27
  18. 18. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 19 tissuesuggestthatinflammationmaycontributetotraumatic cellular and vascular injury.28 Intra- and perivascular accumulation of polymorphonuclear leucocytes occurs approximately 24 hours after injury. This is followed by a delayed phase of inflammation dominated by macrophage infiltration, peaking at approximately 3–5 days.29 The macrophages can secrete a range of factors, including cytokines,tumour necrosis factor and interleukin (IL)-1 and IL-6,which may contribute to the release of free radicals and increase capillary permeability by changing the blood–brain barrier. Conversely, some aspects of the neuroinflammatory response may be involved in promoting repair.30,31 Metabolic changes Cerebral oxidative metabolism (cerebral metabolic rate for oxygen (CMRO2)) remains depressed by approximately 50% in comatose head injury patients for the first 2 weeks after a severe head injury. The degree of depression has been shown to be correlated with long- term outcome.32 Changes in glucose metabolism after acute head injury follow a triphasic pattern. An early, brief hyperglycolytic phase may reflect increased energy demands in attempting to reverse ionic imbalances. This is followed by a‘metabolic depression’ phase that may last up to 30 days after injury. The third stage is gradual recovery.33 In damaged regions of the brain, lactate levels increase as a result of anaerobic metabolism. CONSEQUENCES OF THE EVOLUTION OF CELLULAR DAMAGE Vulnerability of Partly Damaged Cells Partially damaged cells are more vulnerable to secondary brain insults. Brain parenchymal cells need a high rate of energy production to maintain cell integrity and the ionic gradients needed for impulse generation. The oxygen and glucose requirements of brain tissue are higher than those of most other organs and energy stores are limited. These features account for the extreme vulnerability of brain parenchymal cells to ischaemia. Any further insults to partially damaged cells in the immediate postinjury period, particularly hypoxia, focal ischaemia or reduced cerebral perfusion pressure, may acceleratetheadversecascadesof changesandresultincelldeath. Ischaemia may also occur as a result of vasoconstriction that follows severe hypocapnia (reduced PaCO2 ) or vasospasm. Ischaemia is also aggravated by the increased metabolic demands of injured cells as a result of seizures or pyrexia. It is important to realise that most secondary ischaemic insults in the early postinjury period are preventable. Cerebral Oedema Accumulation of water in neurones and glial cells results in cellular swelling (cytotoxic oedema). This is considered to be one of the principal factors contributing to increased intracranial pressure in the early postinjury period.34,35 Cytoprotective Therapy As knowledge developed of the sequential changes following head injury, several pharmacological ‘neuroprotective’ agents were developed and underwent clinical trials. These included free radical scavengers, glutamate antagonists and calcium channel blockers. None has proven beneficial at the time of printing. Clearly, a proven ‘neuroprotective’ therapy would be a major breakthrough in head injury management.36 Damage to the Cerebral Vasculature Damage to the cerebral microvasculature may lead to: (i) narrowing and distortion of the capillary lumen by swelling of capillaryendothelialcells,extrinsiccompressionof capillaries from swollen glial cells, increased leucocyte adherence to capillary endothelium and sludging of red cells; (ii) disruption of the blood–brain barrier, resulting in transendothelial passage of water, ions and protein-rich fluid into the extracellular space (vasogenic oedema); (iii) pericapillary haemorrhage, which may coalesce and enlarge, contributing to the progression of the haemorrhagic component in cerebral contusions; and (iv) loss of autoregulation or vasoparalysis, with vasodilatation and hyperaemia (congestive brain swelling) (Fig. 2.13a, b).26,35 a (b)b ▲ Figure 2.13 Effects of progression of the initial injury in the microcirculation. (a) Uninjured capillary. (b) Changes in the injured capillary leading to reduced flow in the microcirculation, including narrowing and distortion of the capillary lumen by swelling of capillary endothelial cells (open arrows), extrinsic compression by swollen glial cells (large black arrows), leucocyte adherence to the capillary endothelium (small black arrow) and sludging of red cells (black arrowheads).
  19. 19. CONSEQUENCES OF DAMAGE TO THE MICROVASCULATURE Reduction of Regional Cerebral Blood Flow (Hypoperfusion) Pathological changes in the microvasculature and surrounding glial cells can contribute to regional post-traumatic hypoperfusion.2 The loss of endogenous vasodilators (such as nitric oxide) and liberation of vasoconstrictors (such as endothelin-1) are also thought to contribute to early post- traumatic hypoperfusion.38,39 There may be a significant global reduction in cerebral blood flow during the early postinjury period (especially in the first 6–8 hours) after severe head injury. There may also be focal reductions in blood flow around cerebral contusions and in the cerebral hemisphere underlying acute SDH.5,21,26,37,40–42 Current investigations suggest heterogeneity in the degree of perfusion in different regions of the brain after acute head injury.43 Injured brain cells are particularly vulnerable to any reductionsinperfusion,contributingtothecommonoccurrence of ischaemic cell change in patients after severe head injury.17 Brain Swelling and Increased Intracranial Pressure Extracellular oedema (vasogenic oedema) may result from increased capillary permeability due to disruption of the blood– brain barrier.28 Hyperaemic brain swelling may also result from vasoparalysis and vascular engorgement (hyperaemia). Vasogenic oedema and hyperaemia can contribute to post- traumatic brain swelling (and, hence, increased intracranial pressure) in the later stages of acute head injury. Impairment of Autoregulation Autoregulation is the capacity of the cerebral microvasculature to adjust cerebral blood flow in response to changes in cerebral perfusion pressure or changes in cerebral metabolism. The ability of the cerebral arterioles to change their calibre is termed vasoreactivity. PRESSURE AUTOREGULATION The cerebral perfusion pressure (CPP) is the net force driving arterial blood into the cranial cavity: CPP=MAP–ICP where MAP is mean arterial blood pressure and ICP is intracranial pressure. In the uninjured brain, pressure autoregulation maintains a constant cerebral blood flow (CBF) within a range of CPP between 50 and 150 mm Hg. An increase in CPP leads to vasoconstriction of the arterioles. Conversely, a reduction in CPP leads to vasodilatation. METABOLIC AUTOREGULATION Normally, CBF is coupled to the cerebral metabolic rate; CBF is diminished in patients who are in deep coma, in whom the cerebral metabolic rate is reduced. Conversely, CBF increases with seizures or pyrexia when there is an increase in cerebral metabolism. If CBF falls, there is a fall in tissue oxygen, a fall in pH and an increase in tissue carbon dioxide levels. These metabolic changes stimulate vasodilatation and increase CBF. In a significant proportion of patients with severe head injury, cerebral autoregulation is impaired. The impairment of autoregulation is most evident in the immediate postinjury phase and may improve over time.44–48 The loss of the capacity to increase cerebral perfusion in the face of threats such as hypoxia and hypotension contributes to the increased vulnerability of the injured brain to secondary insults.28,49 The distribution of impairment of autoregulation in the cerebral vasculature may be asymmetric, with the more damaged portion of the brain demonstrating greater impairment.45,46,48 Impaired autoregulation has also been demonstrated in patients after mild and moderate head injury, emphasising the importance of maintaining an adequate cerebral perfusion pressure (CPP) even in patients with less severe injury.21,50 The deleterious consequences of impaired autoregulation are further discussed in Chapter 3. CARBON DIOXIDE REACTIVITY Arteriolar calibre, and hence CBF, is sensitive to changes in the pH in the perivascular spaces of the arterioles and, thus, to changes in arterial CO2 levels. Hypercarbia leads to a fall in pH, arteriolar dilatation and an increase in cerebral blood volume and CBF (potential for increased intracranial pressure). Hypocapnia leads to an increase in pH, arteriolar constriction andadecreaseinCBF(potentialforischaemia).Inmostpatients with severe head injury, CO2 reactivity is temporarily disturbed, but returns to normal within 24 hours. The vulnerability to hypocapnia is especially significant because the damaged vessels in the ischaemic areas of the contusions may retain reactivity to changes in PaCO2 even though pressure autoregulation is lost.5,6 Marion et al.51 demonstrated that CO2 reactivity was increased in the hemisphere underlying acute SDH. Patients with severe, persistent impairment of CO2 reactivity die or remain severely disabled.52 CONSEQUENCES OF DAMAGE TO LARGER INTRACRANIAL VESSELS Haemorrhage Extradural haematoma From injury to dural vessels (middle meningeal artery and vein, other meningeal vessels or the dural venous sinuses). Acute subdural haematoma From rupture of bridging veins, that extend between the dural venous sinuses or less commonly arteries between the dura and brain surface, the sylvian veins. Contusion/laceration-related acute SDH From rupture of cortical arteries or venules, most often with injuries to frontal, temporal poles (‘burst lobes’). Intracerebral haematoma From rupture of deeply situated perforating vessels in the brain parenchyma. Ischaemia Vascular injury and ischaemia may also follow stretching and distortion of brain vessels as a result of mechanical 20 PART II BASIC PRINCIPLES
  20. 20. b a ▲ Figure 2.14 Extradural Haematoma (EDH). (a) A computed tomography (CT) scan demonstrating an EDH, typically located directly beneath the area of impact, as indicated by the overlying scalp haematoma. (b) A CT scan with bone window settings demonstrating a skull fracture (white arrowhead). displacement (brain shift or herniations caused by intracranial hypertension) or as a result of vasospasm secondary to traumatic subarachnoid haemorrhage.2 Ischaemia may also occur from damage to major extracranial vessels (e.g. traumatic dissection, stenosis or thrombosis of the internal carotid artery with distal embolisation) or primary traumatic occlusion of the middle cerebral artery.53 Secondary Brain Injury Traumatic Intracranial Haematomas EXTRADURAL HAEMATOMA Extradural haematoma has been reported in up to 4% of all patients who have a computed tomography (CT) scan after acute head injury and in approximately 9% of all patients who are unconscious at admission. Most EDH occur in the second or third decade, when the dura is less densely adherent to the overlying cranium than in the newborn and elderly and, therefore, more easily stripped from the cranium after an impact. Hence, EDH is rare in the newborn and elderly, in whom the dura is tightly adherent to the cranium.54–56 An EDH is usually located directly beneath the point of impact and is associated with a skull fracture in 66%–95% of instances (Fig. 2.14).55 However, in children <15 years of age, an EDH may occur without skull fracture because the skull is more pliable and can deform without fracturing. Although a blow to the head or a fall has the most potential to cause EDH, motor vehicle accidents, being more common mechanisms of head injury, account for nearly 50% of all EDH. In infants and young children, most EDH result from falls.56 Most EDH occur in the temporal or temperoparietal region (62%–80%), with the frontal area (7%–18%), posterior fossa (4%–11%) and vertex being less common sites.55 The anterior or posterior branches of the middle meningeal vessels are the source of bleeding in approximately 80% of EDH. In vertex and posterior fossa haematomas, a dural venous sinus, diploic veins or other meningeal vessels may be the source. Usually the EDH is confined to the area where the dura was stripped at the initial impact. However, brisk and continued arterial bleeding may produce rapidly increasing pressure within the EDH, resulting in progressive stripping of the dura and a rapidly expanding EDH.54 Associated Lesions Intradural lesions, in particular acute SDH and cerebral contusions, are associated with 27%–38% of EDH.54 The incidence of associated lesions is much higher (50%–70%) in patientswhoarecomatose.57 Associatedlesionsmaysignificantly influence the clinical picture and outcome. Posterior Fossa EDH Extradural haematoma is the most common traumatic intracranial lesion in the posterior fossa and is most often seen during the second and third decades of life.58 There is usually an impact injury in the occipital region and a fracture crossing the transverse, sigmoid or confluence of sinuses. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 21 SUBDURAL HAEMATOMA Subdural haematomas are classified as acute, sub-acute or chronic depending on time of presentation after injury. Acute SDH presents within 48 hours, subacute SDH presents between 48 hours and 2 weeks, whereas chronic SDH presents after 2 weeks.59 Acute Subdural Haematoma Acute SDH has been reported in 11% of all patients with acute head injury and in 21% of those with severe head injury.57 The mechanism of injury responsible for the development of an SDH differs between age groups, with motor vehicle-
  21. 21. related accidents (MVA) being the mechanism in a majority of younger patients and falls accounting for most SDH in the older age group (>65 years). In comatose patients, MVA are the mechanism of injury in 53%–75% of SDH.57 Cerebral atrophy with an increase in the potential subdural space increases the risk of acute SDH in chronic alcoholics and the elderly. The usual source of bleeding is a ruptured bridging vein, although at times a cortical artery may be the source (Fig. 2.7).2 When SDH is associated with a cerebral laceration, damaged pial vessels contribute. When a surface artery is the source of bleeding, rapid deterioration of consciousness may occur, similar to the common presentation of an EDH.60 LESIONS ASSOCIATED WITH ACUTE SDH Unilateral hemisphere ischaemia and swelling Brain compression caused by the SDH may lead to ischaemia in the microcirculation and brain swelling (Fig. 2.15).42 Venous compression may also be a factor. The force that generates the SDH may also be responsible for hemisphere damage and swelling. In some instances, the acute SDH may be very thin, but may be accompanied by significant unilateral hemisphere swelling that accounts for most of the mass effect. Diffuse axonal injury, cerebral contusions and intracerebral haematomas (ICH) Acute SDH may be accompanied by DAI, cerebral contusions and ICH. ‘Burst lobe’ Complicated acute SDH is associated with a laceration of the frontal or temporal lobe and intracerebral bleeding (‘burst lobe’). Solonuik et al. described that 28% of cases of traumatic ICH are associated with an acute SDH.16 Patients with acute SDH and coexistent unilateral hemisphere swelling and/or associated lesions often present with a severe degree of neurological impairment and have the potential for further deterioration. This underscores the need for early intensive management once an acute SDH is detected. Subacute SDH Subacute SDH becomes symptomatic between 48 hours and 2 weeks after injury. These lesions are usually not accompanied by significant associated injury. The haematoma undergoes degradation and is usually a mixture of semisolid and fluid blood at the time of presentation. Chronic SDH Chronic SDH becomes symptomatic 2 weeks or more after trauma and is more commonly seen in the elderly or chronic alcoholics. Chronic SDH is also liable to occur in patients with coagulopathy, chronic epilepsy and those with CSF shunts. The head injury may be of a minor nature or, indeed, there may be no history of a head injury. A chronic SDH is thought to originate from a small asymptomatic SDH that becomes enclosed in a membrane containing numerous fragile, enlarged capillary vessels (macrocapillaries). Continued bleeding and escape of plasma from these fragile capillaries is thought to contribute to gradual enlargement of the haematoma.13 Several layers of membranes may develop and haematomas of different stages of evolution may be evident in one location. Absorption of fluid into the haematoma by osmotic mechanisms may also play a role in enlargement of the lesion. Subdural hygroma This is a collection of CSF that accumulates in the subdural space as a result of tear in the arachnoid allowing CSF to enter the subdural space in a valvular fashion. Effusion of fluid from injured vessels in the meninges or in the underlying parenchyma may also play a role.61,62 The fluid in a subdural hygroma is usually clear and xanthrochromic, although at times it may be blood stained. INTRACEREBRAL HAEMATOMAS A typical traumatic ICH is a well-defined, homogeneous collection of blood within the brain parenchyma in contrast with a cerebral contusion,which is an ill-defined,heterogeneous lesion comprising areas of haemorrhage, partially damaged brain parenchyma and necrotic brain. However, this distinction is not always clear because a contusion with a predominantly haemorrhagic component may appear as a traumatic ICH. Traumatic ICH have been reported in approximately 15% of patients with fatal head injury.63 Solonuik et al.16 reported that 28% of traumatic ICH was associated with SDH and 10% with EDH. Most cases of traumatic ICH result from direct rupture of small vessels within the parenchyma secondary to a contre coup injury. Hence, traumatic ICH are often multiple and most frequently (in 80%–90% of cases) occur in the white matter of the frontal and temporal regions. As a result of the common biomechanical mechanisms involved in their production, ICH may be associated with lobar contusions and SDH, the ‘burst lobe’.33,64,65 22 PART II BASIC PRINCIPLES ▲ Figure 2.15 Acute subdural haematoma (AcSDH). A computed tomography scan demonstrating an AcSDH with ischaemia and swelling of the underlying cerebral hemisphere, contributing to a significant mass effect.
  22. 22. a b ▲ Figure 2.16 Intracerebral haematoma (ICH) secondary to penetrating injury. (a) A computed tomography scan with ‘bone’ window settings demonstrating a narrow area of disruption of the cranium (white arrow) by a penetrating injury; there is also evidence of air in the subdural space (white arrowhead). (b) ‘Brain’ window settings showing an ICH (white arrow). PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 23 Traumatic Basal Ganglia Haematomas Intracerebral haematomas occur in the thalamus and basal ganglia in approximately 3% of patients with severe closed head injury.66 These haematomas are often associated with diffuse axonal injury and are thought to result from shearing of deep penetrating branches of the anterior choroidal and lenticulostriate arteries.67 They are often associated with a poor prognosis. POST-TRAUMATIC INTRAVENTRICULAR HAEMORRHAGE Post-traumatic intraventricular haemorrhage has been reported in as many as 25% of patients with severe head injury. Parenchymal haemorrhages and basal ganglia haemorrhages may extend into the ventricular system. Intraventricular haemorrhage in the absence of parenchymal or basal ganglia haemorrhages is due to tearing of veins in the fornix, septum pellucidum or the choroids plexus and is an indicator of a shearing injury.68,69 TRAUMATIC SUBARACHNOID HAEMORRHAGE Traumatic SAH (tSAH) usually results from shear injury to vessels in the subarachnoid space. In the Traumatic Coma Data Bank Study of patients after severe head injury, 39% showed CT scan evidence of tSAH as hyperdense collections of blood in the cerebral sulci, Sylvian fissures and basal cisterns. The risk of mortality rose nearly twofold when tSAH was evident in the CT scan.70 In addition, tSAH may occur at sites of contact injury as a result of disruption of superficial vessels. HAEMATOMAS IN THE CEREBELLUM AND BRAIN STEM Traumatic haematomas in the cerebellum and brain stem are uncommon, being detected in approximately 3% of patients who have CT scans after acute head injury.71 CEREBELLAR HAEMATOMAS Intraparenchymal haematomas of the cerebellum may develop within areas of cerebellar contusions (which are often a result of direct impact) or may develop after a delay in areas of the cerebellum that appear normal on the initial CT scans.72 Traumatic cerebellar haematomas in children which are often associated with an occipital fracture.73 BRAIN STEM HAEMATOMA Two types of traumatic brain stem haematomas have been described:72,73 (i) those associated with diffuse axonal injury, usually located in the dorsolateral part of the upper brain stem; and (ii) secondary brainstem haemorrhages or Duret’s haemorrhages caused by brain stem compression and distortion associated with increased ICP and brain herniation, usually located centrally in the pons or midbrain. Blumbergs also described brain stem contusions, lacerations in relation to skull base fractures and disruptions at the mesencephalic–pontine, pontomedullary and medullocervical junctions.74 An ICH may also develop beneath the site of impact (e.g. adjacent to a linear or depressed fracture) or as the result of a penetrating injury (Fig. 2.16a, b). The mass effect secondary to a traumatic ICH may increase with time due to perilesional swelling or from continued bleeding. Delayed ICH may develop in regions that appear normal in an early CT scan, underlying the need for repeat scanning in patients with severe head injury, even when the initial scan was normal, whenever there is unexpected deterioration (see Chapter 5, Radiological Evaluation).
  23. 23. PROGRESSION OF INTRACRANIAL HAEMORRHAGIC LESIONS AND DEVELOPMENT OF NEW HAEMORRHAGE Acute head injury is a dynamic process and progressive changes that can lead to an increase of the mass effect and intracranial pressure. These changes are: (i) enlargement of existing mass lesions; (ii) development of new mass lesions; and (iii) progression of brain swelling. French and Dublin75 demonstrated that 52% of patients with acute head injury developed new lesions or progression of known lesions in follow-up CT scans. Gentleman et al.76 demonstrated delayed traumatic intracranial haematomas in 15%–20% of patients with severe head injury. A mass effect secondary to evolution of existing lesions or the development of new lesions is the most common cause of sudden neurological deterioration in patients who may be relatively intact at initial assessment.77–79 Delayed Lesions with Diffuse Brain Injury In a recent study of patients with moderate and severe head injury whose initial CT scan showed evidence of a diffuse injury, one of six showed evidence of deterioration in a subsequent CT scan. A new mass lesion was evident in 74% of patients who showed CT evidence of deterioration, worsening prognosis.80 Delayed Lesions After Normal Initial CT Scans The incidence of delayed lesions after a normal initial CT scan, is low (4%–9%) in current studies of comatose patients when high-resolution CT scanners are used.80,81 Mechanisms responsible for delayed haemorrhage in patients with acute head injury include the following.82–87 Delayedruptureofbloodvesselspartiallydamagedduring initial injury This may be precipitated by an increase in intravascular pressure secondary to vasodilatation following loss of autoregulation or as a result of hypoxia or hypercarbia. Surges in blood pressure in restless patients or restoration of blood pressure in a hypotensive patient may also contribute. Release of tamponade effect This may follow a rapid decrease of ICP after surgical removal of a large intracranial haematoma or administration of a bolus dose of intravenous mannitol or excessive CSF drainage. Coagulopathy secondary to brain injury This is discussed in the next section of this chapter. Disseminated coagulopathy Disseminated coagulopathy may occur after severe trauma or as a result of premorbid coagulopathy (e.g. due to anticoagulant medication, alcohol intoxication or liver dysfunction). The lesions most likely to show delayed enlargement are cerebral contusions, ICH and EDH.73,88 Delayed enlargement of EDH Approximately 25% of EDH enlarge in the postinjury period, within a mean interval of 8.2 hours from injury to reaching their final size (range 6–36 hours after injury).89–91 Approximately 8% of EDH appear after an initially negative CT study.92 Delayed enlargement of acute SDH Delayed development of acute SDH is considered rare, with some small acute SDH reported to disappear or decrease in volume.88 However, delayed enlargement of acute SDH has been reported after restoration of blood pressure in hypotensive patientsandafterevacuationof largetraumaticintracranial haematoma.83 Acute SDH in the posterior fossa may enlarge during the first 4 days after injury, especially when it is associated with parenchymal cerebellar injury.93 Delayedenlargementofcerebralcontusions Mostcerebral contusions increase in size or appear as new lesions during the first 12 hours (Fig. 2.13b, c).88 The maximal mass effect due to new haemorrhage and swelling usually occurs at 3–5 days, although this may range from the first 24–48 hours to 10 days or, rarely, even up to 3 weeks after an injury.8,12–14 Statham et al.17 demonstrated that most patients with bifrontal contusions show evidence of progression by 3 days postinjury, but some deteriorate as late as 9 days after injury. Delayed traumatic ICH Delayed traumatic ICH (DTICH) is defined as an ICH that develops in an area of the brain that was non-haemorrhagic on a previous CT scan.13,56,57 Since the advent of CT scanning, it has been recognised that ICH may develop hours to days or even weeks after an acute head injury, even though an immediate postinjury CT scan may not show their presence.9,94 Although a 3.5% incidence of DTICH has been reported among all head- injured patients, the reported incidence in patients with moderate and severe head injury is 3.3%–7.4%.9,56,76 COAGULOPATHY SECONDARY TO BRAIN INJURY Coagulation consists of conversion of fibrinogen to fibrin by a cascade of enzymatic changes initiated by tissue and/or vascular injury.The strands of fibrin trap blood cells (platelets) to form a clot.Coagulationitself,aswellasplateletactivity,releasesaseries of inflammatory mediators that promote further coagulation. Brain tissue is very rich in thromboplastin. The release of tissue thromboplastin by brain parenchymal damage and the damaged endothelium of the cerebral vasculature, as well as platelet activation, can lead to hypercoagulation, fibrinolysis and a depletion of clotting factors locally in the brain. The consumption of coagulation factors is reflected by changes in coagulation parameters: elevation of prothrombin time (PT), activated partial thromboplastin time (APTT), decreased serum levels of fibrinogen and increased serum levels of fibrin degradation products (FDP) and D-dimer. These changes are found to peak at about 6 hours after the injury and return to normal values at 24–36 hours.95 Deleterious Consequences of Coagulopathy Secondary to Brain Injury Increased risk of post-traumatic haemorrhage Delayed, as well as progressive, post-traumatic haemorrhage has 24 PART II BASIC PRINCIPLES
  24. 24. been linked to abnormalities of brain injury induced coagulopathy.86,96 Intravascular microthrombosis and cerebral ischaemia Microthrombi leading to ischaemic brain damage have been demonstrated in rats with fluid percussion injury, pigs with diffuse axonal injury and in contused brain tissue removed from patients with acute head injury during surgical decompression.95 Aggravation of postinjury inflammatory changes Blood coagulation can result in an excessive release of inflammatory mediators, such as cytokines, which can damage parenchymal cells and the vascular endothelium directly, leading to aggravation of ischaemic brain injury.97 Post-traumatic Brain Swelling Brain swelling implies an increase in ‘brain bulk’. This can result from an increase in brain tissue water (brain oedema), an increase in intravascular blood volume (hyperaemia or vascular engorgement) or a combination of both mechanisms.4 Traumatic brain oedema is considered to contribute most to post-traumatic brain swelling.35 TRAUMATIC BRAIN OEDEMA The two principal types of traumatic brain oedema are cytotoxic oedema (intracellular oedema) and vasogenic oedema. Cytotoxic (Intracellular) Oedema Cytotoxic oedema results from the intracellular accumulation of water in neurones and glia. Primary damage to parenchymal cells leads to energy depletion, failure of the active ion pumps and increased permeability of the cell membrane to sodium and water, leading to accumulation of sodium and water in the cells.Cytotoxic oedema can also be aggravated by ischaemia and hypoxia.98 Astrocytes outnumber neurones and can swell up to five times their normal size. Hence, glial swelling is considered the main contributor to cytotoxic oedema.98,99 Vasogenic Oedema Vasogenic oedema is the accumulation of fluid in the extracellular space. Primary injury to the microvasculature can lead to disruption of the blood–brain barrier, with increased capillary permeability and escape of protein-rich fluid from the intravascular compartment into the extracellular space. Vasogenic oedema is seen around cerebral contusions.26 Other important, although less common, mechanisms of traumatic brain oedema include the following. Osmotic oedema (osmolar swelling) Osmotic oedema develops as a result of osmotic imbalances between extracellular and intracellular compartments, leading to entry of water into cells. Such an imbalance occurs in areas of contusion necrosis when macromolecules are broken down into smaller molecules.11,50 Osmotic oedema may also occur as a result of a reduction in the osmolarity of the extracellular space, in hyponatraemia. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 25 Interstitial oedema due to obstructive hydrocephalus An obstruction to CSF outflow results in the accumulation of water in the extrcellular space in the periventricular region. Hydrostatic oedema Hydrostatic oedema may follow an increase in intravascular pressure in an intact vascular bed when loss of autoregulation is combined with high systemic blood pressure or after surgical decompression. Earlier studies suggested that early post-traumatic brain swelling was mainly due to vascular engorgement and an increase in blood volume. Cellular swelling (cytotoxic oedema) was thought to play a minor role.100,101 However, more recent studies suggest that cytotoxic oedema is the main mechanism of traumatic brain oedema and that cytotoxic oedema can develop during the first 24 hours after injury.26,34,35,98 Diffusion- weighted MRI in patients with severe head injury and early post-traumatic brain swelling demonstrated high levels of water content in brain tissue,102 even in those patients without evidence of ischaemia, indicating that cellular swelling was predominantly responsible for early post-traumatic brain swelling. The blood volume was actually reduced after severe traumatic brain injury. An experimental study with contrast- enhanced MRI demonstrated a lack of blood–brain barrier opening during an early phase of rapid brain swelling after diffuse brain injury, excluding a role for vasogenic oedema in early post-traumatic brain swelling.103 CEREBRAL HYPERAEMIA (VASCULAR ENGORGEMENT) Cerebral vasodilatation or hyperaemia leads to brain swelling as a result of increased volume in the intravascular compartment. Such vasodilatation may be the result of the effects of the initial injury or the result of secondary insults, such as hypoxia, hypercarbia, hyperthermia or seizures. Vascular engorgement can also follow an increase in venous pressure as a result of posture, coughing, straining or high intrathoracic pressure. DISTRIBUTION OF BRAIN SWELLING Brain swelling may be focal, unilateral hemispheric or diffuse. Focal brain swelling This is typically seen around cerebral contusions and intracerebral haematoma (shown in Fig. 2.13a). In the initial stages, the swelling may be predominantly cytotoxic, whereas in the later stages of the injury, vasogenic oedema also plays an important role.104,105 Unilateral hemispheric swelling Swelling of an entire cerebral hemisphere most commonly occurs in association with an acute SDH (less commonly with an EDH or without a mass lesion; shown in Fig. 2.15). When such swelling occurs very rapidly, vascular engorgement may play a role, although eventually the predominant factor responsible appears to be cytotoxic oedema.26 Diffuse brain swelling Diffuse brain swelling may develop after a severe diffuse brain injury or may follow secondary
  25. 25. 26 PART II BASIC PRINCIPLES brain insults, such as hypoxia and hypotension. Diffuse brain swelling is seen in approximately 17% of children with severe head injury.105 In most children, such swelling follows a benign course, unless associated with hypoxia and hypotension.106 Diffuse brain swelling also occurs in approximately 12% of adults after severe head injury.106,107 The deleterious effects of brain swelling include increased ICP, reduced cerebral perfusion, cerebral ischaemia and brain shift, if asymetrical; these aspects will be discussed further in Chapter 3 (Harmful Effects of Increased ICP). Focal Brain Damage Secondary to Brain Shifts and Herniations Focal damage may occur secondary to brain shifts and herniations caused by space-occupying haematomas and brain swelling. Such damage includes, most importantly, brain stem compression, focal damage due to compression by brain shifts and focal areas of ischaemia secondary to compression of intracranial arteries. These lesions will be described further in Chapter 3 (Harmful Effects of Increased ICP). Secondary Brain Insults Secondary brain insults can occur at any time after the initial injury as a result of systemic or intracranial pathophysiological disturbances (Table 2.1). Secondary Insults due to Extracranial Causes Secondary brain damage due to extracranial causes is mostly preventable (see Table 2.1). HYPOXIA AND HYPOTENSION Hypoxia (PaO2 <65 mm Hg, O2 saturation <90%, apnoea or cyanosis before admission) and hypotension (systolic blood pressure (SBP) <90 mm Hg in adults) are the most common extracranial causes of secondary ischaemic brain insults. Hypotension after acute head injury is most commonly due to blood loss and should be assumed so until proven otherwise. However, a small subset of patients has hypotension of neurogenic origin.108,109 Hypotension may occur at any time after injury, including: (i) the prehospital period, from the moment of injury to admission to the Emergency Department; (ii) the early postinjury period, during management in the Emergency Department; and (iii) the late postinjury period in the Intensive Care Unit or in the Head Injury Care Ward. Several investigations have highlighted the incidence of hypoxia and hypotension during these different phases and their impact on the outcome of acute head injury (see Table 2.2). As noted previously in the section on initial injury and its progression in this chapter, the injured brain is profoundly vulnerable to hypotension and hypoxia. Hypotension and hypoxia also lead to cerebral arteriolar dilatation (hyperaemia), which, in turn, results in increased ICP. ANAEMIA Anaemia (haematocrit less than 30%) reduces the oxygen- carrying capacity of the blood and can contribute to ischaemic brain injury.116 HYPERPYREXIA Each 1°C increase in temperature results in a 10% increase in oxygen consumption in the brain, thus increasing the risk of ischaemic brain damage. Pyrexia also causes cerebral vasodilatation and increases ICP by 3–4 mm Hg for every 1°C increase in temperature.117 HYPERGLYCAEMIA The sympathoadrenal response to trauma can result in an increase in glucose production. There is experimental evidence that high serum glucose can exacerbate secondary brain injury by increasing lactic acid production, changing neuronal pH and increasing the release of excitatory amino acids.118–120 In patients with severe head injury, hyperglycaemia during the early postinjury period has been shown to be associated with poor outcome.121 SEIZURES Seizures can aggravate the neurochemical and metabolic disturbances in partly damaged brain cells, increase the oxygen demand of cells and lead to an increase in cerebral blood flow with the risk of increased ICP. Table 2.1 Types of secondary brain insults Extracranial insults Intracranial insults Hypoxia (PaO2 <60 mm Hg, O2 saturation <90%, apnoea or cyanosis before admission) Hypotension (SBP <90 mm Hg for adults) Hypocapnia, hypercapnia Acute anaemia (haematocrit <30%) Hyperpyrexia (temperature >38°C) Hyponatraemia (serum sodium <130 mmol/L) Hypoglycaemia, hyperglycaemia Sepsis Increased intracranial pressure, brain shifts and herniations Intracranial haematoma• Cerebral contusion• Brain swelling• Hydrocephalus• Traumatic vasospasm Seizures Intracranial infection Meningitis• Brain abscess• SBP, systolic blood pressure.
  26. 26. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 27 Table 2.2 Hypoxia and hypotension after acute head injury Study Phase Evidence References 131 patients with severe head injury Prehospital On admission to Emergency Department Hypoxia in 27%• Hypotension in 18%• 110 25 patients with acute head injury Prehospital Hypoxia evident in 44%, associated with poor outcome 111 49 patients with acute head injury Prehospital Hypoxia in 55%, hypotension in 24% Threefold increase of poor outcome in hypoxic patients Hypotension associated with poor outcome 112 The National Traumatic Coma Data Bank Study of 717 patients with severe head injury Prehospital, early and late postinjury phases Prehospital and Early Post-injury Hypotension in 34.6% of patients Late post-injury hypotension in 32% A single episode of hypotension nearly doubled the risk of mortality. Patients with untreated hypotension in the prehospital phase fared worse Hypotension developed only during treatment in the ICU in 16.3% of patients 109, 113 107 patients with severe head injury Early postinjury phase Hypotension in 24% of patients Mortality 65% in hypotensive patients Even brief episodes of hypotension are associated with poor outcome 114 81 patients with severe head injury Early and late postinjury phase (first 24 hours after injury) Secondary insults occur mostly in the first 24 hours after injury Hypotension is associated with increased mortality Hypoxia is associated with a longer stay in the ICU 115 ICU, intensive care unit. Ischaemic Brain Damage Following Acute Head Injury Ischaemic brain damage is the predominant pathological change in patients who die from acute head injury.1,122 The mechanisms leading to post-traumatic ischaemic brain damage are listed in Table 2.3. A global reduction of blood flow can occur within the first few hours after severe brain injury, which is mostly coupled to a reduction in the cerebral metabolic rate.2,40,41,122 However, in approximately 30% of patients with severe head injury, the CBF is reduced to ischaemic levels (<18 mL/100 g per min).41 It has been suggested that compromise of the microvasculature is the most likely cause of early ischaemia in severe head injury.26,124 The role of intravascular microthrombosis in ischaemic brain damage has already been discussed. Global ischaemic damage can also result from secondary insults, such as hypoxia, hypotension, increased ICP (leading to diminished cerebral perfusion), anaemia, seizures and hyperthermia, especially in patients in whom the CBF is already reduced. MECHANISMS BY WHICH ISCHAEMIA INFLICTS BRAIN TISSUE DAMAGE The brain is considered to be dependent on aerobic glycolysis and, hence, an adequate supply of oxygen and glucose, which Table 2.3 Causes of ischaemic brain damage in acute injury40–42,123 Global ischaemic damage Focal ischaemic damage Injury to the microvasculature, intravascular microthrombosis Hypoxia, hypotension Increased ICP Intracranial haematoma (EDH, SDH, ICH)• Cerebral contusion• Brain swelling• Anaemia Increased metabolic demands (seizures, hyperthermia) ‘Ischaemic penumbra’ around cerebral contusions Hemispheric ischaemia (hemisphere underlying acute SDH) Brain shifts and herniations leading to focal ischaemic damage in the: Uncus, parahippocampal gyrus• Cingulate gyrus, anterior cerebral artery territory• Posterior cerebral artery territory• Brain stem• Subarachnoid haemorrhage and vasospasm ICP, intracranial pressure; EDH, extradural haematoma; SDH, subdural haematoma; ICH, intracerebral haematoma.
  27. 27. again is dependent on adequate perfusion. The reduction in the cerebral metabolic rate after severe head injury can protect the injured brain from reduced blood flow. Although there is evidence of increased glucose metabolism in the immediate postinjury period, increasing the potential for ischaemic damage, other mechanisms may mitigate the deleterious effects of reduced blood flow. Recent evidence indicates that lactate released into the extracellular space following glucose metabolism in the astrocytes and glia may be metabolised aerobically by the neurones, a phenomenon termed ‘coupled lactate metabolism’.26,127 However, blood flow reduced below a critical ishaemic threshold can interfere with energy dependent functions, such as mitochondrial function, cell membrane integrity, impairment of energy dependant ionic homeostasis in brain cells and propagation of deleterious biochemical cascades, in a manner similar to that occurring in partly damaged cells after the traumatic injury.26 Cerebral ischaemia results in cerebral vasodilatation and further increases in ICP, a reduction of cerebral perfusion pressure and further ischaemia. Brain shifts and herniations secondary to increased intracranial pressure may also result in further ischaemic damage. Patients with mild and moderate head injury who suffer significant ischaemic insults risk adverse outcomes similar to those with severe head injury.128 FOCAL ISCHAEMIC LESIONS Focal ischaemic lesions include: (i) an ischaemic zone around cerebralcontusionsorandICH;(ii)ischaemiainthehemisphere underlying an acute SDH (Fig. 2.15); (iii) arterial vascular territory ischaemia; (iv) venous infarction; and (v) watershed ischaemia. Arterial Vascular Territory Ischaemia Posteriorcerebralarteryterritory Thisisthemostcommon arterial vascular territory ischaemia involves the posterior cerebral artery and is secondary to uncal herniation, which compresses the artery against the tentorial edge, leading to a distal ischaemic lesion in the occipital lobe. Anterior cerebral artery territory Less commonly, the pericallosal branch of the anterior cerebral artery may be compressed between the herniating cingulate gyrus and the free edge of the falx cerebri during lateral transtentorial herniation, resulting in a distal ischaemic lesion, typically located along the medial aspects of the frontal and parietal lobes. Territory of major intracranial vessels An injury to the extracranial internal carotid artery, such as a dissection, may manifest as ischaemia predominantly in the middle cerebral artery territory. Suspicion of such a lesion is an indication for an angiographic study of the extracranial vessels. 28 PART II BASIC PRINCIPLES Venous Infarction Fractures (especially depressed fractures) overlying a major venous sinus can lead to sinus thrombosis and areas of venous infarction. Such infarcts typically appear as irregular haemorrhages located in the white matter in a non-arterial distribution.73 With superior sagittal sinus thrombosis, such areas of haemorrhagic ischaemia may be located in the parasagittal regions; however, the pattern is quite variable. Watershed Ischaemia Severe hypotension in the postinjury period can lead to ischaemia of the junctional zones (watershed areas) between the major intracranial vessel territories. These areas are in the frontal parafalcine region (the watershed between the anterior and middle cerebral artery territories) and in the parietal convexity region (the watershed between the middle and posterior cerebral artery territories).73 Mechanisms Contributing to Repair of Damage from the Initial Injury Intrinsic neuroprotective factors produced by neurones and glia may play an important role in attenuating the effects of the initial injury.129 Neurotrophic growth factors, such as nerve growth factors, brain-derived neurotrophic factor, insulin- like growth factor, glial-derived neurotrophic factor and neurotrophic factor 3, may be upregulated by injury and may aid in recovery. There is experimental evidence that growth factors protect neurones against insults, such as energy loss and glutamate or calcium excess.130 Role of Genetic Profile in Determining the Outcome of Head Injury Genetic factors may also play a role in the outcome of head injury. The apolipoprotein E (ApoE) genotype has been demonstrated to influence the outcome of head injury. Apolipoprotein E is thought to mediate protective mechanisms against secondary oxidative damage to neurones after head injury. Experimental evidence suggests that ApoE deficiency may increase vulnerability to increased cerebral cortical lipid peroxidation and protein nitration.21,130 In neuropathological studies of patients who die from head injury, deposits of amyloid β-protein in the cerebral cortex (a pathological marker of injury severity) have been demonstrated predominantly in patients with the APOE ε4 allele. It has also been suggested that, in patients who survive head injury, those with the APOE ε4 genotype are more than twice as likely to have an unfavourable outcome compared with patients without the APOE ε4 genotype, even when other prognostic factors, such as age, coma score and CT findings, are taken into account.21,74
  28. 28. PATHOPHYSIOLOGY OF ACUTE NON-MISSILE HEAD INJURY CHAPTER 2 29 SUMMARY The initial, or primary, injury results from a mechanical deformation of brain parenchymal cells, axons and the microvasculature. The processes initiated by this injury may continue to damage parenchymal cells, axons and the microvasculature, progressing over several hours or days. Secondary brain damage in the form of intracranial haematoma, brain swelling and increased intracranial pressure can develop during the course of the injury. Damaged brain tissue is vulnerable to further ischaemic insults. This vulnerability is most marked in patients with severe head injury, but extends across the entire spectrum of head injury severity. Secondary brain insults, especially hypoxia, hypotension and increased ICP, can amplify the primary damage and its progression by causing ischaemic brain damage. The outcome of a given injury is determined by a complex interaction between the severity of the initial injury, the pattern of progression, the deleterious effects of secondary brain insults and the processes of healing and repair. There is an increasing recognition of the role of the genetic profile in influencing the course of these complex, interacting processes.