Neuropathology of Abusive Head Trauma

45

CHAPTER 45  NEUROPATHOLOGY OF ABUSIVE HEAD TRAUMA

413

Neuropathology of Abusive Head Trauma Lucy B. Rorke-Adams, MD

INTRODUCTION Injuries from abusive head trauma (AHT) most frequently occur in infants less than 2 years of age.1-3 Infants beyond 1 month to 2 years of age are most vulnerable. In general, younger infants tend to be injured by shaking and/or blunt trauma.4 Lethal shaking of a child older than 3 years of age is more difficult, since neck muscles and spinal ligaments are better developed by that time, and the child can more effectively resist the attack. In neonates, when abuse is suspected, intracranial and spinal injuries caused by birth must be distinguished from inflicted trauma.5-8 Clinicians and pathologists faced with decisions about whether abuse has occurred have an awesome task, since an affirmative decision has serious legal implications and a profound effect on the future of the putative perpetrator. It is incumbent upon the professionals charged with making the judgment to use all available investigative, clinical, and pathological findings before arriving at a decision. The pathologist must be privy to all available information regarding circumstances leading to injury, hospitalization, clinical course, and diagnostic studies. Even though there is suspicion that the death was unnatural, he or she should approach the case with objectivity. Pathologists are “friends of the court,” in that their primary responsibility is to thoroughly establish the postmortem findings and relate them to the investigative and clinical facts. Judkins et al9 published a detailed protocol for examining the central nervous system (CNS) in unexpected child death cases. The forensic pathologist will examine and document all external and internal injuries, separating those findings consequent to treatment.

NEUROPATHOLOGICAL FINDINGS CNS lesions resulting from accidental and inflicted trauma are basically similar; a decision regarding in which category they belong rests upon the historical and clinical aspects of the case and pattern of lesions. When there is an uncontested history of a serious accident, the decision is generally noncontroversial. In contrast, if events leading to a sudden, life-threatening collapse of an apparently well infant/child are vague or inconsistent with the severity of the injury, a decision regarding accidental versus nonaccidental trauma is a greater challenge. Examination and documentation of findings by the neuropathologist should include a thorough external and internal examination of the face, head, and

neck, including soft tissues, bone, meninges, brain, spinal cord and nerves, and eyes.

External Examination Lethal CNS injury can occur in the absence of recognizable external soft tissue damage,10 as in infants whose death is ascribed to shaking alone. (This issue of the significance of shaking and impact in AHT is discussed in Chapter 41, “The Case for Shaking,” and Chapter 43, “Neck and Spinal Cord Injuries in Child Abuse.”) Soft tissue bruises, contusions, and/or lacerations involving face, eyes, ears, head, back, or indeed any other part of the body in infants who are not yet crawling or walking should arouse suspicion of inflicted trauma. Such injury can occur from burns (e.g., hot water, cigarettes), bites, or patterned lesions produced by objects. Establishing the age of the soft tissue injury is a difficult issue, details of which can be found elsewhere.11,12

Internal Soft Tissue Injury Internal soft tissue injury can be present even when no external injury is apparent. Most commonly, this consists of hemorrhages in the deep layers of the scalp, galea, and periosteum (Figure 45-1). Hemorrhages in temporalis muscles, cervical musculature, or back musculature can be found consequent to blunt trauma; lacerations are characteristic if a sharp object has been used. Periosteal hemorrhage can be present with or without an associated fracture.

Fractures The majority of skull fractures in children result from accidental falls, are not usually associated with significant clinical symptoms, and do not require treatment.13 More complex skull fractures occur in serious accidental or inflicted trauma. In the latter instance, they occur when the victim’s head is either struck forcefully by a hard object or is itself struck against the hard object. In infants, striking of the head onto an object is a more common mechanism. Fracture frequency varies from 25% to 40% in victims of inflicted trauma.14-16 A study by Coats and Margulies17 of the material properties of human infant skull and sutures determined that the infant skull can undergo dramatic shape changes before fracture, hence allowing for substantial deformation of the brain. 413

414

SECTION VI  ABUSIVE HEAD TRAUMA

FIGURE 45-3  Inner surface of cranial cap of a 7-month-old abused infant showing sutural diastasis resulting from severe brain swelling and increased intracranial pressure. FIGURE 45-1  Galeal and periosteal hemorrhages on paramedian and left parietooccipital skull of a 3-month-old abused infant.

Spinal fractures are rare, even when significant whiplash injury has occurred; however, if present, they are most easily identified by radiological study.18 In severe shaking there is subluxation rather than fracture of vertebrae, a phenomenon that cannot be identified postmortem.

Intracranial Hemorrhage The most common pathological finding in infants and children who have sustained inflicted neurotrauma is hemorrhage. It is found in one or more of the spaces or potential spaces surrounding brain and spinal cord or within parenchyma, although these are less frequent. In the majority of cases, the hemorrhages are not in and of themselves life threatening, but rather serve as markers that trauma has occurred. At the same time, the pathogenesis of intracranial hemorrhage might be unrelated to trauma, since it can result from coagulopathies, leukemia, certain metabolic disorders, or even ruptured vascular malformations.19-24 Under these circumstances, the hemorrhages are most often parenchymal or in an unusual extraparenchymal location. FIGURE 45-2  Left complex parietooccipital fractures in a 4-month-old infant whose head was struck against a bathroom vanity.

Fractures are most commonly located in the parietooccipital bones but can be anywhere. When they extend into the base of the skull, it can be concluded that the force exerted was considerable. The entire thickness of the skull is ordinarily affected, but unless the dura is stripped, a fracture can be missed (Figure 45-2). Sutural diastasis results from massive brain swelling and rarely from blunt trauma, and should be distinguished from fractures (Figure 45-3).

Epidural Hemorrhage (EDH) If present, EDH is most commonly found in the posterior fossa in association with fracture of the occipital bone, and around the rostral cervical cord and foramen magnum when the victim has been shaken vigorously or subjected to blunt trauma. Blunt trauma to more caudal levels of the back can also lead to EDH. In addition, spinal EDH is often seen in premature newborns who have cardiopulmonary insufficiency, resulting from back pressure in the venous system. These must not be confused with inflicted injury.

CHAPTER 45  NEUROPATHOLOGY OF ABUSIVE HEAD TRAUMA

415

FIGURE 45-4  The brain partially covered by dura (posterior seven eighths of brain) of a 3-month-old abused infant. Note epidural hemorrhage overlying sagittal sinus and spreading laterally posteriorly. Note tension of dura beneath which is a severely swollen brain. This is protruding above the surface of the cut border of the dura anteriorly. The dura on the right has a bluish cast—a characteristic color when there is underlying blood. Note the small amount of subdural blood at anterior dural edge on the left.

FIGURE 45-6  Skull base of same infant pictured in Figures 45-2 and 45-5. Note pooling of subdural blood along left side of the anterior and middle fossae. Note also acute hemorrhages in olfactory grooves bilaterally (arrow).

FIGURE 45-5  The brain of the 4-month-old infant with the fractures pictured in Figure 46-2. Note extensive subdural blood pooled in the cranial cap that has been reflected (and patchy subdural blood over the vertex of the brain bilaterally), subarachnoid hemorrhage, and severe brain swelling.

EDH in the supratentorial cavity is most often seen along the sagittal sinus and is usually associated with subdural hemorrhage (Figure 45-4). Elsewhere, it is typically, but not always, associated with temporal bone fracture, a rarity in infants and children.25 If this occurs, however, it can be concluded that the amount of force applied to the head was extraordinarily strong, since without it, the dura, which is the functional periosteum of the inner table of the skull, would not separate from the bone. Subdural Hemorrhage (SDH) The characteristic CNS lesion in victims of AHT is SDH.14,26-28 This hemorrhage can be unilateral or bilateral, is often paramedian, and most abundant in the posterior interhemispheric fissure (Figure 45-5). Blood can also pool

along the roof of the orbits or floor of the middle fossa (Figure 45-6). The volume of subdural blood generally is not sufficient to require surgical drainage, although in rare cases, it can be a large space-occupying lesion, and if not evacuated promptly, leads to death from increased intracranial pressure. When consequent to a tear of the vein of Galen, the bulk of the blood is located in the region of the quadrigeminal plate/pineal gland, and can extend into the posterior fossa as well. Subdural blood often surrounds the spinal cord in traumatized individuals, and the issue of its origin can be problematic. If SDH is identified in the supratentorial space, some have assumed that the blood can be transported by gravity to the caudal levels. This assumption is untenable, since it is not possible for the blood to gain access to the posterior fossa or spinal subdural space; the tentorium, brainstem, and cerebellum block exit from the supratentorial space. Instead, subdural blood, which typically originates at the vertex of the brain, can only fall by gravity to the skull base in the anterior and middle fossa, where it is often seen (see Figure 45-6). Still, subdural blood originating in the posterior fossa has easy access to the spinal subdural space if the foramen magnum is not blocked by a swollen brainstem and herniated cerebellar tonsils. Hence, if blood is found around the cord, origin is either local (i.e., from primary trauma to the back) or from trauma affecting the posterior fossa structures (Figure 45-7). It is the majority opinion among experts involved in diagnosis and treatment of individuals with CNS trauma that SDHs result from tearing of bridging veins that normally

416

SECTION VI  ABUSIVE HEAD TRAUMA

FIGURE 45-7  Posterior view of spinal region of a 7-week-old abused infant showing acute, extensive epidural/subdural hemorrhages.

FIGURE 45-8  Vertex of left hemisphere of a severely battered 3-year-old child. The dura has been retracted to show an intact bridging vein entering the sagittal sinus. Subdural clots are located more anteriorly and are located at the vertex of the hemisphere and in the interhemispheric fissure.

leave the subarachnoid space to enter the sinuses (Figure 45-8).29 Although all bridging veins are vulnerable to tearing, those most commonly affected are located at the vertex of the brain that enter the sagittal sinus. In severe trauma, the sinus itself can be torn. The leaves of the falx cerebri, which are formed by two apposed sheets of dura, can contain hemorrhage of variable size; the dura, which itself consists of two layers, typically contains hemorrhage within its substance in trauma-induced SDH. Intrafalcine and tentorial hemorrhages are not uncommon in newborns or neonates and are associated with the birth process (Figure 45-9).7 Some claim that blood in the subdural space originates within the dura or falx and then leaks into the space, a major cause of such hemorrhage being hypoxia, but this novel suggestion by Geddes et al30 was withdrawn 4 years following publication,31 and the literature contains no scientific support from other investigators for this hypothesis.

FIGURE 45-9  Falx cerebri of a 3-day-old infant who died consequent to complication of a diaphragmatic hernia. This was an incidental finding.

It has also been asserted that a subdural space does not exist.32 If such were the case, there could be no entity called “subdural hematoma,” and the pathologist would always be forced to remove a brain encased in dura. Moreover, if the dura were attached to the arachnoid, that membrane would be torn in the process of separating the dura and brain. This simply never occurs unless earlier inflammation has led to formation of adhesions binding the two. The anatomical and biomechanical factors that underlie the pathogenesis of subdural hematomas are outlined as follows: (1) the dura is firmly attached to the inner table of the skull, since it is the functional periosteum of the bones, and hence does not move, (2) in certain regions of the skull, two separate leaves of dura come together to form sinuses, of which the most important in this context is the superior sagittal sinus, (3) in order for the cerebral veins to drain into the sinuses, they must leave the protection of the leptomeninges and traverse the space between the arachnoid and the sinus, which is the subdural space, (4) under the normal activities of daily living there is no problem. However, if a force is exerted on the head and the brain is free to move, but the dura containing the sinuses is fixed, then movement of brain places stress on the veins and causes them to tear. The torn veins are sometimes identified during surgery; Maxeiner33 has outlined a technique that allows postmortem identification.33,34 Since subdural blood is most often of venous origin, it is dark red-purple in the fresh state, and the hematoma is often described as a “currant jelly clot.” Arterial tears also occur but are uncommon.33 For an in-depth discussion of the biomechanics of shaking and pathogenesis of subdural bleeding, see Morrison and Minns.35 If left undisturbed and the individual survives, the blood is encapsulated by formation of a two-layered membrane. The outer membrane is composed of fibrous granulation tissue and is adjacent to the dura, whereas the denser fibrous tissues comprising the inner membrane is adjacent to, but separate from, the arachnoid. Vasculature in the outer membrane can bleed, but the volume of such hemorrhaging is not often clinically important, even though this mecha-

CHAPTER 45  NEUROPATHOLOGY OF ABUSIVE HEAD TRAUMA

417

SAH of nontraumatic origin can result from venous thromboses, coagulopathies of various types, vasculitides of inflammatory or obscure origin, or rupture of a vascular malformation or aneurysm (giant or mycotic). SAH unaccompanied by SDH or other features suggestive of trauma is most likely a consequence of natural disease.19-24 Parenchymal/Intraventricular Hemorrhage

FIGURE 45-10  Organized subdural membrane showing fibrosis and striking neovascularization. The infant was abused at 5 weeks of age and died of pneumonia 11 months later (H&E stain ×100).

nism is all-too-often invoked to explain sudden collapse of an otherwise apparently normal infant (Figure 45-10). In particular, defense experts postulate that infants sustain a primary subdural bleed days or weeks before they present with life-threatening symptoms. The experts claim that the acute event is consequent to a re-bleed from an organized hematoma. Such an argument is unsound because the primary hematoma would have to be quite large in order to produce a membrane with sufficiently abundant vascularity to cause to a re-bleed of large enough volume to result in clinical symptoms. It is unlikely that such a large original hematoma would remain clinically silent and that a secondary bleed would result in catastrophic collapse and/or death. Furthermore, a re-bleed would occur over a period of time, during which symptoms of CNS dysfunction would become apparent. Medical attention would most likely be sought before the complications of increased intracranial pressure became irreversible. Finally, postmortem examination would reveal the offending membrane and re-bleed, along with evidence of mass effect, unilateral cerebral compression, and the attendant herniation that are the pathological hallmarks of such an event. In reality, such findings are rare in infants with putative AHT. At the same time, an isolated postmortem finding of a thin subdural membrane or hemosiderin in the dura or leptomeninges should not necessarily excite suspicion of inflicted trauma. Small subdural, intradural, intrafalcine/ tentorial, and subarachnoid hemorrhages are common postmortem findings in infants who die of a variety of non-CNS disorders, are most likely associated with the birth process, and are of no clinical significance.6-8 Subarachnoid Hemorrhage (SAH) SAH of various sizes (usually small) and distribution frequently accompany SDH and are the result of bleeding from small arteries in the subarachnoid space; they can be distinguished from subdural blood of venous origin by their bright red color.26 Because of their small size, they might not be visualized on radiological studies (see Figure 45-5).

Parenchymal hemorrhages of traumatic origin are typically small and most commonly associated with gliding contusions, callosal tears, and primary brainstem trauma. If isolated or large, their origin is more likely caused by a coagulopathy, venous thrombosis, or rupture of a vascular malformation. Parenchymal hemorrhage arising either in the CNS or elsewhere in the body while the infant/child is under medical surveillance should alert the clinician to the possibility that a natural disease rather than trauma is the likely cause. If blood is found in the occipital horns and there is no obvious source of hemorrhage in the cerebrum, the possibility that it originated from a vertebral artery tear must be seriously considered and investigated. Under these circumstances, a small amount of blood is usually present around the caudal brainstem and adjacent cervical spinal cord. The blood in these regions and the occipital horn represents anterograde flow from the primary site of injury.

Cerebrospinal Contusions/Lacerations By definition, contusions/lacerations (C/L) are caused by trauma. Theoretically they can occur at any superficial and/ or deep site and can be isolated or numerous. In reality, the majority exhibit a well-recognized distribution pattern that often allows the pathologist to reconstruct the likely events that produced the injury. When superficial, they are easily identifiable, since they typically contain hemorrhages. They extend into underlying cortex and sometimes white matter for a variable distance. There are three major categories of C/Ls: coup, contrécoup, and intermediate coup. The first two types are generally located superficially, whereas the latter can only be diagnosed after the tissue has been sectioned. Intermediate coup injury is not always accompanied by significant hemorrhage, and microscopic study might be necessary to recognize it. C/Ls occur at the time of the primary trauma. Localization of the lesions is dependent upon biomechanical factors. Specifically, if the moving head strikes a hard object such as in a simple fall in which the back of the head hits the ground, the coup lesion (involving neural tissue immediately below the impact site of the skull, specifically occipital lobes) will be minimal or absent, whereas the portion of brain in a line opposite the impact site will exhibit contrécoup injury, namely of the orbital surfaces of frontal lobes and temporal poles. On the other hand, if a moving object strikes the stationary head, the coup lesion in the brain below the impact site will be more severe than the contrécoup injury 180 degrees opposite to the primary blow. There may or may not be a fracture in either instance. Intermediate coup lesions can arise consequent to either angular or linear acceleration.

418

SECTION VI  ABUSIVE HEAD TRAUMA

FIGURE 45-11  Acute contusions/lacerations and subarachnoid hemorrhage involving cerebral gyri of 1-month-old abused infant.

Superficial Contusions/Lacerations Superficial C/Ls in infants/children with AHT most commonly involve the olfactory bulbs and tracts and are typically produced by shaking or other forces producing angular acceleration. If, on the other hand, the head has been subjected to blunt trauma, either by being hit by some object or by being struck against a hard surface, the location of the C/Ls will be related to the specific features of the injury. Repetitive trauma can cause C/Ls of different ages. Recognition of these lesions is straightforward, since acute lesions are hemorrhagic and display disruption of surface tissue that may or may not be swollen, depending upon survival time after injury (Figure 45-11). In the subacute stage, swelling recedes as there is retraction of tissue and the color of the lesion changes while hemoglobin breaks down into hemosiderin, which is a brownish green-gold (Figures 45-12 and 45-13). Long-standing lesions are typically retracted and more golden than brown, reflecting further transformation into hematoidin.

FIGURE 45-12  Vertex view of cerebral hemispheres of an 8-weekold infant who was subjected to repeated blunt trauma to the head. Note organized contusions/lacerations bilaterally (left greater than right) and more recent hemorrhages.

Deep Contusions/Lacerations Included in this group are intermediate coup lesions. These are often localized to the temporal and insular cortex in individuals who have sustained trauma to lateral regions of the skull, and tend to occur in pedestrians or bicyclists struck by vehicles or those thrown from vehicles; they are rarely seen in infants or children with AHT. In contrast, the most common deep lesions found after abusive infant head trauma are consequent to shearing forces produced by angular acceleration, and tend to occur in particular sites, such as cerebral white matter, corpus callosum, internal capsule and other fiber tracts at various levels, and in the rostral pons at the level of the locus ceruleus; they are infrequently found in cerebellar white matter. In especially violent trauma the ependyma can tear, allowing fragments of brain tissue to enter the ventricle. These are identifiable on microscopic study, especially in the aqueduct where they become stuck. The majority of the deep C/Ls in infants and children fall into two groups: gliding contusions and axonal injury.

FIGURE 45-13  Base of brain of an 18-month-old infant showing organization of contusions/lacerations of olfactory bulbs (arrows).

CHAPTER 45  NEUROPATHOLOGY OF ABUSIVE HEAD TRAUMA

419

FIGURE 45-14  Coronal section through mid-cerebrum of a 1-year-old female showing gliding contusion on left. This is extending from the surface of the superior frontal convolution into the white matter. Note small residual hemorrhage.

Gliding Contusions/Lacerations. In contrast to those in superficial sites, deep C/Ls are not ordinarily associated with a significant amount of hemorrhage. Gliding contusions consist of dorsoventral slits in paramedian cerebral white matter and are most often found in the frontal lobes, but they can occur at any level if traumatic forces are unusually severe (Figures 45-14 and 45-15). Lesions of this type were described by Lindenberg and Freytag,36 who suggested that they resulted from shearing forces acting upon the gelatinous, unmyelinated white matter of the infant. White matter of the developing brain, which is unmyelinated for the most part, has a much higher concentration of water than exists in the fully mature brain, and hence is more vulnerable to tears. Lesions in the same locations are common in older children and adults who sustain closed head injury in bicycle, motorcycle, vehicular, or pedestrian trauma. These lesions have more prominent hemorrhages than those seen in the infant, and frank cavitation of tissue occurs only in exceptional circumstances. Microscopic findings are a function of the age of the injury. In the early stage, the tissue cleft contains some red blood cells along the margin and a few inflammatory cells (see Figure 45-15). After 24 hours, inflammatory cells are more abundant, gitter cells with and without hemosiderin become an important component of the inflammatory reaction, and astrocytic proliferation at the margins becomes apparent. In the chronic stage, a sharply demarcated cavity marks the site of injury (Figure 45-16). Other white matter lesions, aside from axonal injury (see below) consist of edema associated with acute swelling of oligodendroglia, the nuclei of which are sometimes pyknotic and/or karyorrhectic (Figure 45-17). Focal and general neuroinflammatory response consequent to diffuse traumatic brain injury includes activation of resident microglia and macrophages recruited from peripheral circulation and can be evaluated by use of immunohistochemical procedures for expression of CD163 or CD68.37

FIGURE 45-15  Photomicrograph of gliding contusion in frontal lobe of a 1-month-old infant. Note split in the tissue and presence of hemorrhage (H&E stain ×100).

FIGURE 45-16  Coronal section through frontal lobe of a 4-year-old child who was abused at 4 months of age. Note the large, sharply demarcated cavity on the right side. This has replaced most of the white matter on that side.

The more elegant techniques, such as confocal or electron microscopy at the disposal of laboratory investigators, are not feasible in the majority of young victims of AHT because of varying degrees of autolysis consequent to respirator therapy. Of all CNS fiber tracts, the corpus callosum is the most frequent target of injury, although identification of the lesions is often difficult if the victim has been on life support for more than 24 hours. The lesions are characterized by

420

SECTION VI  ABUSIVE HEAD TRAUMA

FIGURE 45-17  Acutely swollen oligodendroglia in edematous, damaged white matter (arrows) (H&E stain ×100).

FIGURE 45-18  Coronal section through the cerebrum at the level of the corpus striatum. Note small hemorrhage in corpus callosum just to the right of midline.

tears and petechial or larger hemorrhage, most commonly in the posterior third of the body and splenium. It is good practice to gently separate the hemispheres while the brain is in situ to determine gross evidence of such injury. If autolysis is advanced, identification might be impossible. Recognition of callosal injury is easier on examination of coronal sections, and varies from total to partial transection with or without injury of the adjacent cingulate gyrus. If partial, it is always localized to the dorsally placed fibers (Figures 45-18 and 45-19). Premortem damage is usually accompanied by hemorrhages along the torn edges. On the other hand, linear, horizontally, or irregularly oriented hemorrhages are sometimes seen unassociated with a gross tear. Occasionally, callosal damage becomes apparent only on microscopic study and can be localized anywhere along the callosum or at its junction with the centrum ovale (Figure 45-20). A focal contusional-type lesion localized to the ventrolateral brainstem in infants and children whose head has been subjected to violent angular acceleration, consequent to either repeated blunt trauma or shaking, consists of complete, or more often, incomplete subpial necrosis. This is characterized by fragmentation of neuropil, a variable

FIGURE 45-19  Photomicrograph of the corpus callosum of an 8-week-old infant who arrived at the hospital dead on arrival. Note tissue fractures and hemorrhage in center of corpus callosum. The cingulate gyrus is just dorsal to the callosum (H&E stain ×10).

FIGURE 45-20  Hemisection of corpus callosum and cingulate gyrus just above lateral ventricle and caudate nucleus of a 9-month-old infant. Note the dark brown irregular expression of β-amyloid precursor protein (β-APP) at lateral edge of callosal fibers at their junction with the centrum ovale (arrows) and torn central fibers of callosum (immunoperoxidase technique for expression of β-APP ×10).

number of retraction balls (see below), accumulation of lipidladen macrophages, and acutely swollen, sometimes necrotic, oligodendroglia with or without petechial hemorrhages (Figure 45-21). It rarely occurs in subpial regions of cerebral gyri. Axonal Injury. Axonal injury consequent to head trauma was first described by Strich38 over 50 years ago. It results from exertion of powerful forces causing angular acceleration or impact injury; it is not necessarily lethal unless localized within brainstem structures controlling cardiorespiratory functions. At the same time, however, axonal damage in the cerebrum can have a profound effect on psychomotor function if the victim survives. Axonal injury occurs at the time of the primary trauma, and progresses thereafter.29 It is not solely caused by trauma but is associated with vascular and metabolic events.38-44 In the infant, nontraumatic axonal injury is most commonly seen in white matter necrosis as a result of perfusion injury, primarily in prematurely born neonates, a disorder known as periventricular leukomalacia.45 Such lesions have characteristic

CHAPTER 45  NEUROPATHOLOGY OF ABUSIVE HEAD TRAUMA

FIGURE 45-21  Acutely swollen oligodendroglia, some of which are pyknotic, in subpial ventral pontine tissue (arrows) (H&E stain ×100).

FIGURE 45-22  Retraction balls in centrum ovale of an abused 4-month-old infant (arrows) (H&E stain ×100).

clinical and pathological features that are not likely to be confused with trauma. When consequent to abusive head injury, axonal damage is most commonly found in corpus callosum and fiber tracts in cerebrum, brainstem, and spinal cord, as well as in cranial and spinal nerve roots. If there is vascular damage, associated hemorrhage is present. Axonal injury in the upper outer quadrant of the pons at the level of the locus ceruleus is typically associated with hemorrhage and parenchymal damage and hence can often be diagnosed on gross examination. Although it has been noted that axonal injury is almost universal in individuals who die following head injury, it is difficult to diagnose unless survival has been greater than 2 hours, although it may be presumed if there is hemorrhage.40 In those who survive 18 to 24 hours, the routine H&Estained sections contain small, eosinophilic, round structures called retraction balls (Figure 45-22). It is often possible to recognize axonal swelling, but a more precise assessment of axonal injury can be made if a silver staining technique, such

421

FIGURE 45-23  Swollen, damaged axons in midbrain of a 4-monthold abused infant (immunoperoxidase technique for expression of Beta APP ×600).

as Bodian’s, is used.46 Currently it is preferable to use immunohistochemical techniques to look for expression of β-amyloid precursor protein (β-APP); antibodies for neurofilament protein expression in axons can also be used (Figures 45-20 and 45-23).47,48 When axonal damage results from ischemia or metabolic disturbances, it can be difficult to distinguish from that induced by trauma, especially if located in cerebral or cerebellar white matter.43,44 If other features of frank infarction are present, it is not generally problematic, or if it is located in fiber tracts (i.e., corpus callosum, internal capsule, descending tracts in brainstem, spinal cord white matter, or nerve roots) as isolated ischemic necrosis in these regions, it is rare. Tissue autolysis that occurs after cerebral circulation has ceased but the individual is maintained on life support (“respirator brain”) does not cause axonal injury. As noted, use of the antibody CD163 for identification of macrophages is helpful in evaluating the parenchymal lesions in all categories.

Brainstem and Spinal Injuries While there are many ways of inflicting injury to an infant, among the more common is shaking and impact. Shaking usually precedes the impact, which typically involves striking the head against a hard object. On the other hand, postmortem study of some infants reveals no evidence of blunt trauma to scalp or skull, and although it is conceivable that the head was impacted against a soft surface (e.g., mattress or cushions), the possibility that only shaking was involved is likely.35 Some perpetrators describe what they did (e.g., only “shook the infant”),49 and it is entirely possible to produce serious injury by shaking alone, the mechanism being that of a whiplash phenomenon.26,27,50,51 Every parent knows that the heavy head of the infant must be supported until structures in the neck are sufficiently developed to allow independent head control, usually by about 8 to 12 months of age when the baby is at least able to sit without support.52 The upper two cervical vertebrae of the infant are particularly mobile because spinal ligaments are not well developed, hence the cervical spinal cord is

422

SECTION VI  ABUSIVE HEAD TRAUMA

FIGURE 45-24  Section of rostral pons showing multifocal primary hemorrhagic contusions in the tegmentum and basis pontis of a 3-year-old girl subjected to multiple blows to the head (arrows) (H&E stain ×5).

especially vulnerable to damage if the neck is hyperextended. Such injuries to the cervical cord have, in fact, been documented in complicated deliveries.53 In traumatic whiplash—whether accidental or inflicted— brainstem, rostral spinal cord, nerve roots, vertebral arteries, and soft tissues are all potential targets for injury. Fractures are uncommon, since the bony involvement is typically subluxation; soft tissue damage is not often conspicuous. Occasionally the caretaker of an infant in whom there is an allegation of abuse will report that the infant developed breathing difficulty and became limp following shaking. Even without such an admission, it is obvious that this combination of symptoms is characteristic of spinal shock.54 Because the whiplash injury typically involves caudal brainstem and rostral cord, it is absolutely necessary to follow the dissection procedure described by Judkins et al.9 If this is not done, the lesion(s) can be missed. The lesions are typically hemorrhagic and can be found in many different sites, including brainstem, vertebral arteries, meninges, nerve roots and ganglia, and spinal cord (Figures 45-24 and 45-25). Hemorrhages can be epidural, intradural, subdural, or subarachnoid. Axonal damage involving roots and spinal cord is most easily identified when studied for expression of ß-APP. Spinal cord C/Ls typically include partial parenchymal tears or complete transaction (Figures 45-25, 45-26, 45-27, and 45-28). Lesions consisting primarily of acute neuronal necrosis or frank infarction are more likely as a result of cardiorespiratory failure and shock than direct trauma. It should be understood that any level of spinal cord and/ or surrounding structures can be traumatized by mecha-

FIGURE 45-25  Primary hemorrhagic contusions/lacerations of cervicomedullary junction of an abused infant.

FIGURE 45-26  Photomicrograph of cervical spinal cord showing hemorrhagic contusions/lacerations (H&E stain ×5).

nisms other than whiplash, such as slamming or hitting the victim’s back against a hard object, or forceful beating. In rare instances, forceful blows to the top of the head will produce C/L of the central tissue of the spinal cord.

Traumatic Brain Injury/Edema/Swelling Primary damage to nerve cells and blood vessels occurs consequent to mechanical forces of sufficient magnitude,

CHAPTER 45  NEUROPATHOLOGY OF ABUSIVE HEAD TRAUMA

423

FIGURE 45-29  Cerebrum (in situ) of an abused 3-year-old showing severe brain swelling characterized by gyral widening and flattening and sulcal attenuation. Note severe superficial congestion and subarachnoid hemorrhage.

FIGURE 45-27  Photomicrograph of cervical spinal nerve roots surrounded by abundant subdural and intradural hemorrhage from a 1-month-old abused infant (H&E stain ×40).

45-29). Uncal/parahippocampal grooves are rare in infants because the cranial sutures are still open. On the other hand, the posterior fossa of the infant is a more confined space, since its roof is the tentorium, and the only opening is the foramen magnum, which has a fixed diameter, even in an infant. The tentorial notch is, of course, filled with the brainstem. The brainstem and cerebellum are often swollen, either primarily because of primary injury (brainstem) or as a result of vascular compression. If severe, this often leads to necrosis of cerebellar tonsils, which, when the infant is maintained on a respirator, become autolytic and float into the spinal subdural and/or subarachnoid space. Durét hemorrhages do not occur in infants; hence if brainstem hemorrhages are present, the most likely pathogenesis is trauma. The intra vitem autolysis that occurs after the brain tissue has already died, but the infant is maintained on a respirator hinders, but might not totally obviate, microscopic study.

Anoxic Encephalomyelopathy/ Infarction FIGURE 45-28  Acute hemorrhage in dorsal root ganglion in an abused 3-month-old infant (H&E stain ×40).

and then as a result of complicated cascades of membranous and biochemical events. Breakdown of cell membranes, endothelial injury, and disturbance of blood–brain barrier all contribute to general brain dysfunction aside from the more obvious C/Ls and axonal injury, and most likely play a major role in pathogenesis of edema and swelling.29 Edema and swelling of the brain are commonly present if the infant survives for several hours after injury.55-58 Details of the complex, multifactorial pathogenesis are presented in elegant detail by Blumbergs et al29 and Minns and Brown.59 If the infant dies, the brain swelling is characterized by gyral widening and flattening and sulcal effacement (Figure

At least 75% of abused infants and children exhibit hypoxicischemic lesions of brain and/or spinal cord.58 Gross and microscopic features are generally not difficult to identify, and although pathophysiological features overlap, hypoxic lesions will be discussed separately from those that are ischemic. Hypoxic Lesions When the partial pressure of arterial oxygen decreases to a critical level, the phenomenon of cerebral autoregulation is set in motion.60 Cerebral arteries dilate and capillary beds open to allow for maximal flow as a compensatory mechanism for inadequate oxygen delivery to the tissues. If severe, the cardiac muscle, which is also deprived of oxygen, begins to fail, thereby leading to ischemia. Ensuing neuronal/ parenchymal necrosis precipitates brain swelling. This may

424

SECTION VI  ABUSIVE HEAD TRAUMA

FIGURE 45-30  Coronal section through midcerebrum showing classical dark pink gray matter characteristic of acute anoxic encephalopathy.

be accentuated by traumatic brain injury described previously and is often diagnosed by neuroimaging studies.61-64 Pathological features of severe asphyxia from any cause, including accidental or homicidal smothering, are often striking, since dilatation of the vascular bed consequent to autoregulation is prominent, both in subarachnoid and parenchymal vessels. Because the arterial pO2 is decreased and the pCO2 is elevated, the usual light pink color of grey matter is transformed into a peach or purple color, depending upon the severity of the asphyctic state, since the pCO2 in the arteries is more similar to that normally carried by veins (Figure 45-30). Infants who have been smothered are often regarded as victims of so-called SIDS. Hence, if the pathologist is unaware of the pathophysiology of asphyxia and color changes just described, that error is easily made. In particular, the brain of an individual of any age who dies suddenly does not display the congestion and discoloration of the asphyctic brain with the possible exception of cases of “nearmiss SIDS.” If the individual dies within a short time, the expected microscopic lesions associated with acute anoxia might not be recognizable. Ischemic Lesions Individuals who have a sudden cardiac arrest and/or shock, but who are resuscitated and survive for a variable length of time thereafter, exhibit a unique pathological picture that was described and named “hypotensive brainstem necrosis” by Gilles et al.65 This circumstance typically causes global necrosis, but the gross pathological features of the brainstem are particularly striking. There is obvious duskiness of inferior colliculi, pontine and medullary tegmentum, and olivary and dentate nuclei produced by vascular dilatation and congestion, consequent to reflow into damaged regions (Figure 45-31). Hypotensive brainstem necrosis may occur at any age and should not be confused with primary brainstem trauma. Infarction resulting from severe ischemia can occur anywhere in the brain and/or spinal cord, the extent being a function of the length and severity of the insult. Microscopic

FIGURE 45-31  Transverse section of medulla and cerebellum. Note the striking dusky brown color of the medullary tegmentum (arrow) characteristic of hypotensive brainstem necrosis.

FIGURE 45-32  Photomicrograph of organizing infarction 2 weeks after the ictus in a 2-month-old abused infant (H&E stain ×200).

features of grey matter necrosis in the infant are sometimes more exaggerated than those occurring in adults if the infant survives for a week or more, since the infarcted regions often contain an extraordinary number of fat-laden macrophages (gitter cells), some of which may be multinucleated (Figure 45-32).

Chronic Lesions All victims of inflicted neurotrauma, even those with severe injury, do not necessarily die immediately. In those who survive for months or years, the separation of traumatic injury from hypoxic-ischemic damage can be challenging (Figure 45-33). Subdural membranes are often present and are recognizable without difficulty. Although severe surface scars and deep gliding contusions are not problematic, retraction balls and damaged axons months or years after the primary event are not ordinarily identified.

Optic Nerve and Retinal Injury Injuries to the optic nerve and retina are common in infants who are victims of inflicted neurotrauma.4,10,66-70 At the same

CHAPTER 45  NEUROPATHOLOGY OF ABUSIVE HEAD TRAUMA

425

FIGURE 45-33  Coronal section through frontal lobes of infant who was abused at 2 months of age but died 10 months later. Note replacement of normal cortex and white matter by cysts and the golden color of tissue, especially on the left side.

FIGURE 45-35  Photomicrograph of an optic nerve, disc, and posterior portion of retina of a 4-month-old abused infant showing extensive subdural and retinal hemorrhages that occupies all layers (H&E stain ×10).

FIGURE 45-34  Globes with attached optic nerves from a 7-week-old abused infant. Note acute hemorrhages extending from the junction of the globe and nerve.

time, pathogenesis of these lesions is a controversial issue. (See Chapter 44, “Eye Injuries in Child Abuse.”) Forensic study of an infant or child who has died of trauma, accidental or inflicted, must include examination of the eyes: globes, optic nerves, surrounding meninges, and soft tissue. The most prominent findings consist of hemorrhage in and beneath the dura surrounding the optic nerve as well as retinal hemorrhage. Optic nerve sheath hemorrhages are typically located at the junction of the nerve and globe and extend toward the brain for a variable distance. Although these are most often found within the dura and subdural space, it is not unusual to identify them in epidural soft tissues and subarachnoid spaces. The optic nerve is ordinarily not damaged directly (Figures 45-34 and 45-35). In contrast, the retina is a common target for injury, incidence ranging from 50% to 100%, but the most frequent figure is 80%.10,69,71 Only one or both eyes can be affected.

FIGURE 45-36  Photomicrograph of a retina showing extensive retinal, preretinal, and vitreous hemorrhage of a 7-week-old abused infant (H&E stain ×40).

Retinal hemorrhages extend from the disc, often symmetrically, for a variable distance toward the ora serrata and can involve one or more, sometimes all, layers of the retina (Figure 45-36). When severe, the retina can be thrown into folds or tear, and there can also be vitreous hemorrhage. Folds and tears should be investigated during gross examination since the retina is often separated from the choroid in the process of slide preparation. If the victim survives, organization of the hemorrhages, retinal scarring, and Wallerian degeneration ensue.

426

SECTION VI  ABUSIVE HEAD TRAUMA

MEDICAL EVIDENCE RELATING TO INFLICTED NEUROTRAUMA Abuse of infants and children has been a grim reality throughout the history of mankind, and the type of abuse has involved a wide spectrum, ranging from culturally approved sacrifices to gods, and runs the gamut of starvation, abandonment, burning, smothering, drowning, shaking, beating, and throwing from buildings, over cliffs, or against objects. Aside from physical means, including widespread sexual abuse, more subtle and difficult to define psychological trauma to children has been, and is, all too common.72 In 1942, John Caffey focused attention on a constellation of features that he called “whiplash-shaken baby syndrome.” This included traumatic injury of the nervous system, with or without bony injuries, and retinal hemorrhages.73,74 In the ensuing 62 years an enormous body of literature has become available documenting social, clinical, and pathological features of infants and children alleged to have been victims of abuse. A considerable proportion of this literature consists of case reports ranging from one to many examples of putative inflicted trauma and falls into the category of clinical research. This has been a time-honored method for sharing observations of medical issues with colleagues and has formed the cornerstone of medical knowledge throughout centuries. Indeed, journals devoted to human diseases affecting various organ systems have, do, and will in future publish peer-reviewed papers that fall into the category of clinical research. In this venue, physicians worldwide have reported their experiences in dealing with clinical problems similar to those described by Caffey, such that there currently exists a mountain of evidence in support of the hypothesis that a recognizable clinical entity does indeed exist produced by severe shaking-battering of an infant. In addition, the forensic literature is replete with reports of postmortem findings of such cases, along with supporting investigative data collected by police.75 The current state of knowledge that has accumulated over the years may thus be summarized as follows: 1. An apparently well infant suddenly experiences difficulty breathing, loss of tone, and unconsciousness. 2. The infant is alone with the caretaker. 3. Although emergency medical personnel might succeed in resuscitation, the infant remains unresponsive, remains ventilator dependent, and often requires vasopressor agents. 4. Evidence of soft tissue trauma and/or fractures might or might not be found. 5. Radiologic studies typically identify a small subdural hematoma, usually in a posterior, paramedian location, with or without evidence of profound hypoxic-ischemic injury, the so-called black brain. 6. Unilateral or bilateral retinal hemorrhages are commonly diagnosed by an experienced ophthalmologist. 7. Postmortem examination discloses a constellation of any or all of the following: soft tissue injury, skull fracture, SDH, SAH, brain swelling, C/Ls (superficial or deep, and in various sites, ranging from brain to spinal cord), axonal injury, hypoxic-ischemic damage, and optic nerve and retinal hemorrhages.

This list does not imply that these features are found in every infant or child that is abused, but only summarizes the common findings amongst this group. Naturally each case is unique, but there is no established natural disease for which this combination of features is diagnostic, other than inflicted trauma. To make this diagnosis, it is absolutely necessary to consider all aspects of the case, since any one or two features could have a nonsuspicious etiology. Into this arena has come a small group of physicians and engineers who aggressively challenge the reality of inflicted neurotrauma in infants and children, claiming that the clinical-pathological features most characteristically found in these victims of abuse are actually a consequence of hypoxiaischemia, increased intracranial pressure, increased intravascular pressure, and excessive coughing.30,76-78 There is no evidence-based literature to support their point of view, but this does not seem to deter them. Even though the clinical-pathological features of inflicted neurotrauma in infants and children are firmly established, there remain questions, such as understanding the biomechanics involved in shaking and the pathogenesis of retinal hemorrhages. It is often claimed that this constellation of abnormalities might result from a short fall, but there is currently considerable evidence to the contrary.59 Inflicted neurotrauma is a uniquely human affliction and for this reason cannot be studied objectively in the laboratory. The current state of knowledge regarding inflicted neurotrauma is well summarized in publications edited by Minns and Brown79 and Reece and Nicholson,80 but it is clear to experts in the field that experimental studies that approximate more closely the human situation must be performed if we are to advance our knowledge of the mechanisms involved in this devastating social, medical, and legal problem.

References 1. Myhre MC, Grøgaard JB, Dyb GA, et al: Traumatic head injury in infants and toddlers. Acta Paediatr 2007;96:1159-1163. 2. Duhaime AC, Alario AJ, Lewander WJ, et al: Head injury in very young children: mechanisms, injury types, and ophthalmologic findings in 100 hospitalized patients younger than 2 years of age. Pediatrics 1992;90:179-185. 3. Keenan HT, Runyan DK, Marshall SW, et al: A population-based study of inflicted traumatic brain injury in young children. JAMA 2003;290:621-626. 4. Budenz DL, Farber MG, Mirchindani HG, et al: Ocular and optic nerve hemorrhages in abused infants with intracranial injuries. Ophthalmology 1994;101:559-565. 5. Nelson JS: Developmental and perinatal neuropathology. In: Nelson JS, Mena H, Parisi JE, et al (eds): Principles and Practices of Neuropathology, ed 2. Oxford University Press, New York, 2003, pp 24-44. 6. Looney CB, Smith JK, Merck LH, et al: Intracranial hemorrhage in asymptomatic neonates: Prevalence on MR images and relationship to obstetric and neonatal risk factors. Radiology 2007;242:535-541. 7. Schwartz P: Birth Injuries of the Newborn. Hafner Publishing, New York, 1961. 8. Rooks VJ, Eaton JP, Ruess L, et al: Prevalence and evolution of intracranial hemorrhage in asymptomatic term infants. AJNR Am J Neuroradiol 2008;29:1082-1089. 9. Judkins AR, Hood IA, Mirchindani HG, et al: Technical communication. Rationale and technique for examination of nervous system in suspected infant victims of abuse. Am J Forens Med Pathol 2004;25:29-33. 10. Morad Y, Kim YM, Armstrong DC, et al: Correlation between retinal abnormalities and intracranial abnormalities in the shaken baby syndrome. Am J Ophthalmol 2002;134:354-359.

CHAPTER 45  NEUROPATHOLOGY OF ABUSIVE HEAD TRAUMA

11. Kornberg AE: Skin and soft tissue injuries. In: Ludwig S, Kornberg AE (eds): Child Abuse. A Medical Reference, ed 2. Churchill Livingstone, New York, 1992, pp 91-104. 12. Hobbs CJ, Hanks HGI, Wynne JM: Child Abuse and Neglect. A Clinician’s Handbook. Churchill Livingstone, London, 2000, pp 73-75. 13. Meadows R. ABC of Child Abuse. BMJ Publications, London, 1989, pp 199-248. 14. Case ME, Graham MA, Handy TC, et al: Position paper on fatal abusive head injuries in infants and young children. Am J Forensic Med Pathol 2001;22:112-122. 15. Geddes JF, Hackshaw AK, Vowles GH, et al: Neuropathology of inflicted head injury in children. I. Patterns of brain damage. Brain 2001;124:1290-1298. 16. DiRocco C, Velardi F: Epidemiology and etiology of cranio-cerebral trauma in the first two years of life. In: Raimondi AJ, Choux M, DiRocco C (eds): Head Injuries in the Newborn and Infants. Springer Verlag, New York, 1986, pp 125-139. 17. Coats B, Margulies SS: Material properties of human infant skull and suture at high rates. J Neurotrauma 2006;23:1222-1232. 18. Kleinman PK, Shelton YA: Hangman’s fracture in an abused infant: imaging features. Pediatr Radiol 1997;27:776-777. 19. Hoffman GF, Naughten ER: Abuse or metabolic disorder? [letter]. Arch Dis Child 1998;78:399. 20. Allison JW, Davis PC, Sato Y, et al: Intracranial aneurysms in infants and children. Pediatr Radiol 1998;28:223-229. 21. Weissgold DJ, Budenz DL, Hood I, et al: Ruptured vascular malformation masquerading as shaken baby syndrome. Surv Ophthalmol 1995;39:509-512. 22. Rutty GN, Smith CM, Malia RG: Late-form hemorrhagic disease of the newborn: a fatal case report with illustration of investigations that may assist in avoiding the mistaken diagnosis of child abuse. Am J Forensic Med Pathol 1999;20:48-51. 23. O’Hare AE, Eden OB: Bleeding disorders and non-accidental injury. Arch Dis Child 1984;59:860. 24. vonKries R, Gobel U: Vitamin K prophylaxis and vitamin K deficiency, bleeding (VKDB) in early infancy. Acta Pediatr 1992;81: 655-660. 25. Bilmire ME, Myers PA: Serious head injury in infants: accident or abuse? Pediatrics 1985;75:340-342. 26. Brown JA, Minns RA: Non-accidental head injury with particular reference to whiplash shaking injury and medico-legal aspects. Dev Med Child Neurol 1993;35:849-869. 27. Duhaime AC, Christian CW, Rorke LB, et al: Non-accidental head injury in infants – the “shaken-baby syndrome.” N Engl J Med 1998;338:1822-1829. 28. Feldman KW, Bethel R, Shugerman RP, et al: The cause of infant and toddler subdural hemorrhage: a prospective study. Pediatrics 2001;108: 636-646. 29. Blumbergs P, Reilly P, Vink R: Trauma. In: Love S, Louis DN, Ellison DW (eds): Greenfield’s neuropathology, ed 8, Vol I. Hodder Arnold, London, 2008, pp 733-832. 30. Geddes JF, Tasker RC, Hackshaw AK, et al: Dural hemorrhage in non-traumatic infants: does it explain bleeding in “shaken baby syndrome”? Neuropathol Appl Neurobiol 2003;29:14-22. 31. Richards PG, Bertocci GE, Bonshek RE, et al: Shaken baby syndrome. Arch Dis Child 2006;91:205-206. 32. Haines DE: On the question of a subdural space. Anat Rec 1991;23:3-21. 33. Maxeiner H: Detection of ruptured bridging veins at autopsy. Forensic Sci Int 1997;89:103-110. 34. Maxeiner H: Lethal subdural bleedings of babies—accident or abuse? Med Law 2001;20:463-482. 35. Morrison CN, Minns RA: The biomechanics of shaking. In: Minns RA, Brown JK (eds): Shaking and Other Non-accidental Head Injuries in Children. Mac Keith Press, Cambridge, 2005, pp 106-146. 36. Lindenberg R, Freytag E: Morphology of brain lesions from blunt trauma in early infancy. Arch Pathol 1969;87:298-305. 37. Kelley BJ, Lifshitz J, Povlishock JT: Neuroinflammatory response after experimental diffuse traumatic brain injury. J Neuropathol Exp Neurol 2007;66:989-1001. 38. Strich SJ: Diffuse degeneration of the cerebral white matter in severe dementia following head injury. J Neurol Neurosurg Psychiatry 1956;19:163-185. 39. LeClercq PD, McKenzie JE, Graham DI, et al: Axonal injury is accentuated in the caudal corpus callosum of head-injured patients. J Neurotrauma 2001;18:1-9.

427

40. Graham DI, Saatman KE, Marklund N, et al: The neuropathology of trauma. In: Evans RW (ed): Neurology and Trauma, ed 2. Oxford University Press, New York, 2006, pp 45-94. 41. Povlishock JT, Becker DP, Cheng CLY, et al: Axonal change in minor head injury. J Neuropath Exp Neurol 1983;42:225-242. 42. Yam PS, Takesago T, Dewar D, et al: Amyloid precursor protein accumulates in white matter at the margin of a focal ischemic lesion. Brain Res 1997;760:150-157. 43. Dietrich WD, Kraydieh S, Prado R, et al: White matter alterations following thromboembolic stroke: a β-amyloid precursor protein immunocytochemical study in rats. Acta Neuropathol 1998;95:524531. 44. Dolinak D, Smith C, Graham DI: Hypoglycemia is a cause of axonal injury. Neuropath Appl Neurobiol 2000;26:448-453. 45. Banker BQ, Larroche J-C: Periventricular leukomalacia of infancy. Arch Neurol 1962;7:386-410. 46. Bodian D: A new method for staining nerve fibers and nerve endings in mounted paraffin sections. Anat Res 1936;65:89-97. 47. Sherriff FE, Bridges LR, Gentleman SM: Markers of axonal injury in postmortem human brain. Acta Neuropathol 1994;88: 433-439. 48. Dolinak D, Reichard R: An overview of inflicted head injury in infants and young children, with a review of β-amyloid precursor protein immunohistochemistry. Arch Pathol Lab Med 2006;130:712717. 49. Starling SP, Patel S, Burke BL, et al: Analysis of perpetrator admissions to inflicted traumatic brain injury in children. Arch Pediatr Adolesc Med 2004;158:454-458. 50. Hadley MN, Sonntag VKH, Rekate HL, et al: The infant whiplashshake injury syndrome: a clinical and pathological study. Neurosurg 1989;24:536-540. 51. Munger CE, Peiffer RL, Bouldin TW, et al: Ocular and associated neuropathologic observations in suspected whiplash shaken infant syndrome. A retrospective study of 12 cases. Am J Forensic Med Pathol 1993;14:193-200. 52. Swaiman KF: Neurologic examination after the newborn period until 2 years of age. In: Swaiman KF, Ashwal S (eds): Pediatric Neurology Principles & Practice, ed 3, Vol I. Mosby, St Louis, 1999, p 32. 53. Adams JH, Cameron HM: Obstetrical paralysis due to ischemia of the spinal cord. Arch Dis Child 1965;40:93-96. 54. Nacimiento W, Noth J: What, if anything, is spinal shock? Arch Neurol 1999;56:1033-1035. 55. Hubschmann OR, Krieger AJ: The pathophysiology of head trauma. J Med Soc N J 1983;3:181-183. 56. McIntosh TK, Smith DH, Meaney DF, et al: Neuropathological sequelae of traumatic brain injury: relationship to neurochemical and biomechanical mechanisms. Lab Invest 1996;74:315-342. 57. David TJ: Shaken baby (shaken impact) syndrome: non-accidental head injury in infancy. J Soc Med 1999;92:556-561. 58. Aldrich EF, Eisenberg HM, Saydjari C, et al: Diffuse brain swelling in severely head-injured children. A report from the NIH Traumatic Coma Data Bank. J Neurosurg 1992;76:450-454. 59. Minns RA, Brown JK: Neurological perspectives of non-accidental head injury and whiplash/shaken baby syndrome: an overview. In: Minns RA, Brown JK (eds): Shaking and Other Non-Accidental Head Injuries in Children. MacKeith Press, London, 2005, pp 1-105. 60. Toole JF: Cerebrovascular Disorders, ed 4. Raven Press, New York, 1990, pp 30-32. 61. Sane SM, Kleinman PK, Cohen RA, et al: Diagnostic imaging of child abuse. Section on Radiology. Pediatrics 2000;105:1345-1348. 62. Lonergan GJ, Baker AM, Morey MK, et al: From the archives of the AFIP. Child abuse: radiologic-pathologic correlation. Radiographics 2003;23:811-845. 63. Tung GA, Kumar M, Richardson RC, et al: Comparison of accidental and nonaccidental traumatic head injury in children on noncontrast computed tomography. Pediatrics 2006;118:626-633. 64. Steinbok P, Singhal A, Poskitt K, et al: Early hypodensity on computed tomographic scan of the head in an accidental pediatric head injury. Neurosurgery 2007;60:689-695. 65. Gilles FH: Hypotensive brainstem necrosis. Selective symmetrical necrosis of tegmental neuronal aggregates following cardiac arrest. Arch Pathol 1969;88:32-42. 66. Andrews A: Ocular manifestations of child abuse. Pa Med 1996;995: 71-75. 67. Greenwald MJ, Weiss A, Oesterle CS, et al: Traumatic retinoschisis in battered babies. Ophthalmology 1986;93:618-625.

428

SECTION VI  ABUSIVE HEAD TRAUMA

68. Giangiacomo J, Khan JA, Levine C, et al: Sequential cranial computed tomography in infants with retinal hemorrhages. Ophthalmology 1988;95:295-299. 69. Kivlin JD, Simmons KB, Lazoritz S, et al: Shaken baby syndrome. Ophthalmology 2000;107:1246-1254. 70. Schloff S, Mullaney PB, Armstrong DC, et al: Retinal findings in children with intracranial hemorrhage. Ophthalmology 2002;109: 1472-1476. 71. Levin AV: Ophthalmic manifestations of inflicted childhood neurotrauma. In: Reece RM, Nicholson CE (eds): Inflicted Childhood Neurotrauma. American Academy of Pediatrics Press, Elk Grove Village, Ill, 2003, pp 128-159. 72. Block H: Abandonment, infanticide and filicide. Am J Dis Child 1988;142:1058-1060. 73. Caffey J: Multiple fractures in the long bones of infants suffering from subdural hematoma. AJR Am J Roentgenol 1946;56:163-173.

74. Caffey J: On the theory and practice of shaking infants. Its potential residual effects on permanent brain damage and mental retardation. Am J Dis Child 1972;124:161-169. 75. Annerbäck E-M, Lindell C, Svedin CG, et al: Severe child abuse: a study of cases reported to the police. Acta Paediatr 2007; 96:1760-1764. 76. Leetsma JE: Case analysis of brain-injured admittedly shaken infants: 54 cases, 1969-2001. Am J Forensic Med Pathol 2005;26:199-212. 77. Squier W: Shaken baby syndrome: the quest for evidence. Develop Med Child Neurol 2008;50:10-14. 78. Talbert DG: Paroxysmal cough injury, vascular rupture and “shaken baby syndrome.” Med Hypoth 2005;64:8-13. 79. Minns RA, Brown JK (eds): Shaking and Other Non-Accidental Head Injuries in Children. MacKeith Press, London, 2005. 80. Reece RM, Nicholson CE (eds): Inflicted Childhood Neurotrauma. American Academy of Pediatrics Press, Elk Grove Village, Ill, 2003.