Introduction
Synonym | Interpretation / perception |
---|---|
Shaken baby syndrome | Trauma mechanism: shaking |
Shaken impact syndrome | Trauma mechanism: shaking and impact |
Whiplash shaken infant syndrome | Trauma mechanism: shaking |
Schűtteltrauma | Trauma mechanism: shaking |
Syndrome du bébé secoué | Trauma mechanism: shaking |
Skakvald | Trauma mechanism: shaking |
Abusive head trauma | Intention: abusive |
Non-accidental head injury | More or less neutral |
Inflicted traumatic brain injury | More or less neutral |
Inflicted head injury | More or less neutral |
Methods
Database search
Article selection
Data extraction
Results
Search results & quality assessment
Studies in lambs
Journal | Journal of Clinical Neuroscience |
Objective | To develop a satisfactory biomechanical model for the pathogenesis of non-accidental head injury |
Animals | 7 lambs + 3 controls (2010 article) [1] - Age matched 7- to-10-day-old, 8.7 kg (5–12) - Age matched 7- to-10-day-old, 8.7 kg (5–12)group 1 (n = 6): ‘older’, 10.3 kg [8.5–12 kg] - Age matched 7- to-10-day-old, 8.7 kg (5–12)group 2 (n = 3): ‘younger’, 5.5 kg [5–6 kg] - Age matched 7- to-10-day-old, 8.7 kg (5–12)controls (n = 4): 7- to-10-day-old, [5–10.5 kg] |
Trauma mechanism | Anesthesia and ventilation. Manually grasped under axilla, vigorously shaken, head back and forth with considerable lateral/rotational movement for 10 × 30 s in 30 min. No head impact. |
Histopathology fixation | 6 h full anesthesia before death by formalin perfusion fixation. Brains remained 2 h (‘overnight’ in 2012 and 2013 articles) in situ and 7 days ex-situ immersed in formalin. |
Outcome measures | Macroscopy and microscopy of brains and rostral cervical spinal cord; 5 mm slices of brain and spinal cord: - β-APP immunohistochemistry and HE-staining (2010 and 2012 articles) - HE-staining, c-fos-staining, and EMA staining. (2013 article) Ocular examinations (2010 and 2012 articles) |
Head and shaking kinematics |
Studies in piglets
Article | Objective | Animals | Trauma mechanism | Fixation | Outcome measures | Input dynamics |
---|---|---|---|---|---|---|
Raghupathi 2002 [6]
Journal of Neurotrauma
Traumatic Axonal Injury after Closed Head Injury in the Neonatal Pig | To better understand the mechanical environment associated with closed pediatric head injury, by animal models including salient features. | 7 piglets + 1 control; 3-to-5-day-old; average weight: 2.0 kg (1.5–3.0, 3 unknown). Average brain weight: 35 g (33–38). | Anesthesia and ventilation. Rapid, inertial, non-impact, transverse head rotation 110° over 10–12 ms, centered in the cervical spine, with HYGE pneumatic actuator. Heads secured to padded snout clamp. | 6–8 h anesthesia and ventilation before death. Heparin perfusion, in situ fixation with 10% formalin, followed by ex-situ fixation overnight. | Macroscopy and microscopy of brain, cerebrum, and brain stem with Nissl staining, NF68 and NF200 immunohistochemistry; ABC-histochemistry. | Angular velocity of 272 rad/s. Average PAV of 250 ± 10 rad/s. |
Raghupathi 2004 [7]
Journal of Neurotrauma
Traumatic axonal injury is exacerbated following repetitive closed head injury in the neonatal pig | To evaluate the effect of reducing the loading conditions on the extent of regional traumatic axonal injury, and to develop a model of repeated mild brain trauma. | 11 piglets + 3 controls; 3-to-5-day-old. Group 1 (n = 5): single rotation (15 ms), ± weight 2.0 kg (1.8–2.4), ± brain weight 36 g. Group 2 (n = 6): double rotation (15 ms, 10–15 m apart), ± weight 2.1 kg (1.7–2.5), and ± brain weight: 35 g. | Anesthesia and ventilation. Rapid, non-impact, transverse rotations of the head centered in the cervical spine, with HYGE pneumatic actuator. Heads secured to padded snout clamp. | 6 h Anesthesia and ventilation before death. Heparin perfusion, in situ fixation with 10% formalin, followed by ex-situ fixation overnight. | Macroscopy and microscopy of brain, cerebrum, and brain stem with NF200 immunohistochemistry, and ABC-histochemistry. | PAV averaging 172 rad/s for single and 138 rad/s for double loads. |
Friess 2007 [8]
Experimental Neurology
Neurobehavioral Functional Deficits Following Closed Head Injury in the Neonatal Pig | To develop reliable quantitative functional neurobehavioral assessments for brain injury in piglets. | 18 piglets + 9 controls; 3-to-5-day-old. Group 1 (n = 10): 1 moderate acceleration (188 rad/s). Group 2 (n = 5): controls moderate group. Group 3 (n = 8): 2 consecutive transverse, mild accelerated (142 rad/s) head rotations, 3.1 ± 0.5 min apart. Group 4 (n = 4): controls mild group. | Anesthesia and ventilation. Single, rapid, non-impact, transverse head rotation with the HYGE pneumatic actuator, 1–3 min after end of isoflurane. Heads secured to padded bite plate. | After 12 days re-anesthetized, death by pentobarbital, heparin and then in situ fixed with 10% formalin. Ex situ fixed overnight. | Macroscopy and microscopy of brain, cerebrum, brain stem, and high cervical spinal cord with HE staining, β-APP staining, and NF68 immunohistochemistry and counterstained with Meyer’s hematoxylin. | Moderate acceleration: 62.90 ± 10.10 krad/s2, velocity: 188 ± 7 rad/s. Mild acceleration: 34.12 ± 2.80 krad/s2, velocity: 142 ± 2 rad/s. |
Friess 2009 [9]
Journal of Neurotrauma
Repeated traumatic brain injury affects composite cognitive function in piglets | To develop a cognitive composite dysfunction score to correlate white matter injury severity in piglets with neurobehavioral assessments. | 21 piglets + 7 controls (7 littermate groups, of 5 piglets); 3-to-5-day-old. Group 1 (n = 7): single. Group 2 (n = 7): double; 1 day apart. Group 3 (n = 7): double; 7 days apart. Group 4 (n = 7): controls. Group 5 (n = 5): controls for group 3 | Anesthesia and ventilation. Moderate (190 rad/s) rapid, non-impact, transverse angle rotation of 110° over 10–12 ms with HYGE pneumatic actuator. Heads secured to padded bite plate. | After 12 days re-anesthetised, death by pentobarbital/heparin, then in situ fixed with 10% formalin. Ex situ fixed overnight. Group 3 and 5 sacrificed after 5 days instead of 12. | Macroscopy and microscopy of brain, cerebrum, brain stem, and high cervical spinal cord with HE staining, β-APP staining, and counterstained with Meyer’s hematoxylin. | Velocity: Gr 1:: 193.7 rad/s, Gr 2: 196.7–195.9 rad/s, Gr 3:: 190.3–187.6 rad/s Acceleration: Gr 1: 58.51 krad/s2. Gr 2: 55.17–54.35 krad/s2. Gr 3: 57.32–56.12 krad/s2 |
Naim 2010 [10]
Developmental Neuroscience
Folic Acid Enhances Early Functional Recovery in a Piglet Model of Pediatric Head Injury | To test if folic acid supplementation after injury would decrease the severity of TAI in our well-established piglet model of moderate pediatric head injury. | 4 groups: 40 female + 10 male piglets, 3-to-5-day-old. Group 1 (n = 7): injured + daily intraperitoneal folic acid injection (IF) 2.24 kg. Group 2 (n = 8): injured + daily saline injection (IS) 2.01 kg. Group 3 (n = 8): uninjured + daily folic acid injection (UF) 1.8 kg. Group 4 (n = 7): uninjured + daily saline injection (US) 1.99 kg. Group 5: behavior controls. | Anesthesia and ventilation. Rapid, inertial, 90–110° transverse rotation, centered in the cervical spine with the HYGE pneumatic actuator. Heads secured to padded bite plate. | After 6 days re-anesthetized, death by pentobarbital, heparin and then in situ fixed with 10% formalin. | Behavioral testing on days 1 and 4 following injury. Macroscopy and microscopy of brain, cerebrum, brain stem, and high cervical spinal cord with HE staining, β-APP staining, and counterstained with Meyer’s hematoxylin. | Angular velocity: IF group: 193.29 ± 5.31 rad/s, IS group: 194.25 ± 8.11 rad/s |
Article | Objective | Animals | Trauma mechanism | Fixation | Outcome measures | Input dynamics |
---|---|---|---|---|---|---|
Ibrahim 2010 [11]
Journal of Neurotrauma
Physiological and pathological responses to head rotations in toddler piglets | To characterize the physiological and pathological responses of the immature brain to inertial forces and their relationship to neurological development. | 13 female piglets; brain weight 56.04 g, 4-week-old. Group 1 (n = 2): controls, Group 2 (n = 4): low rate angular acceleration, Group 3 (n = 6): moderate rate angular acceleration. | Anesthesia and ventilation. Single non-impact, transverse rotation, centered in the cervical spine. Heads secured to padded bite plate with snout straps and pneumatic actuator. | Euthanized 6 h after injury. Death by pentobarbital, in situ perfusion fixation with 10% formalin. Ex situ fixed in 10% formalin. | Macroscopy and microscopy of brain, cerebrum, brain stem, and high cervical spinal cord, with HE-staining, β-APP staining, NF68 and counterstained with Meyer’s hematoxylin. | Acceleration: low (31.6 ± 4.7 krad/s2,) or moderate (61.0 ± 7.5 krad/s2,). PAV: low: 129 ± 13 rad/s, moderate 194 ± 15 rad/s. |
Article | Objective | Animals | Trauma mechanism | Fixation | Outcome measures | Input dynamics |
---|---|---|---|---|---|---|
Coats 2010 [12]
Investigative Ophtalmology & Visual Science
Ocular Haemorrhages in Neonatal Porcine Eyes from Single, Rapid Rotational Events | To characterize ocular hemorrhages from single, rapid head rotations in the neonatal pig. | 51 piglets + 5 controls; 3-to-5-day-old. Group 1 (n = 13): sagittal rotation, Group 2 (n = 7): coronal rotation, Group 3 (n = 31): transverse rotation, Group 4 (n = 5): controls. | Anesthesia and ventilation. Single rapid (15 ms), non-impact head rotation, centered in the C3-C5 spine, with HYGE pneumatic actuator. Heads secured to padded snout clamp. | 6 h anesthesia before death by heparin infusion and in situ fixation with 10% formalin. Ex situ fixed overnight. | Brain macroscopy (46/51 animals), microscopy (31/51): brain, cerebrum, brainstem: HE-staining and NF68 or APP. Indirect ophthalmoscopy, (10 injured +2 controls) and macroscopy, microscopy (HE staining) | Angular velocities and accelerations: 117–266 rad/s and 30.6–101 krad/s2. |
Eucker 2011 [13]
Experimental Neurology
Physiological and histopathological responses following closed rotational head injury depend on direction of head motion | The effect of sagittal and coronal rotation on regional cerebral blood flow changes, unconsciousness times, and apnea incidences, as well as early pathological outcomes. | 36 piglets; 3-to-5-day-old. Group 1 (n = 9) HOR-HIGH: > 90° horizontal (transverse) rotation, Group 2 (n = 7) COR: > 90° coronal rotation, Group 3a (n = 6) SAG: > 60° sagittal rotation, Group 3b (n = 6) HOR-LOW: 90° horizontal (transverse) rotation, Group 4 (n = 4): controls. | Anesthesia and ventilation. A single rapid (12–20 ms), non-impact head rotation, centered at the mid-cervical spine with a bite plate. | Euthanized 6 h after injury. Death by pentobarbital, perfusion fixation/in situ. Fixation with 10% formalin. Ex situ fixed in 10% formalin for over 24 h. | Macroscopy and microscopy of brain, cerebrum, brain stem, and high cervical spinal cord, with HE-staining, β-APP staining and counterstained with Meyer’s hematoxylin. | Group 1: PAV of 198 ± 12 rad/s. Group 2: PAV 208 ± 11 rad/s. Group 3a: PAV 166 ± 3 rad/s. Group 3b: PAV 168 ± 3 rad/s. Group 4: (controls) 0 rad/s. |
Coats 2017 [14]
Journal of Neurotrauma
Cyclic Head Rotations Produce Modest Brain Injury in Infant Piglets | To systematically investigate the post-injury pathological time course after cyclic low-velocity head rotations and compare them with single head rotations. | 50 piglets + 4 controls; 3-to-5-day-old. Group A (n = 5): sagittal, episodic. Group B (n = 6 sagittal, 2 transverse): continuous 30 s. Group C (n = 4): transverse, continuous 10 s. Group D (n = 8): transverse, continuous 30 s. Group E (n = 9): transverse, double continuous 30 s. Group F (n = 5): transverse, continuous 30 s. Group G (n = 5): sagittal, single-noncyclic. Group H (n = 6): sagittal, single-noncyclic. Controls: (n = 2) 6 h + (n = 2) 24 h post-injury. | Anesthesia and ventilation. Non-impact, 30° sagittal or 50° transverse rotations of the head, centered in the cervical spine, with HYGE pneumatic actuator. Heads secured to bite plate; hyperflexion/ extension of the neck was avoided. | Sacrificed 6 h (Group A, B, G, and Controls), 24 h (Group C, D, E, H and Controls) or 6 days (Group F) after last injury. | Macroscopy and microscopy of brain, cerebrum, and brain stem; HE-staining, β-APP staining with Mayer Hematoxylin counterstaining. Eyes: Indirect fundus examination, macroscopy, and HE-staining. | Single axis angular rate transducer; 2–3 Hz. Sagittal: peak-to-peak average angular velocity (unclear how this was determined) 22.71 ± 3.49 rad/s and average peak angular acceleration of 606.21 ± 160.30 rad/s2. Transverse: peak-to-peak angular velocity 28.92 ± 2.85 rad/s and peak angular acceleration 780.08 ± 118.03 rad/s2. |
Article | Group | Intervention | No piglet | angular velocity rad/s (± SD) | angular acceleration krad/s2 (± SD) | SDH (SAH) | PH | Ischemia | AI (β-APP, NF68, or NF200) |
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Raghupathi 2002 [6]: 7 piglets + 1 control; 3-to-5-day-old, 6–8 h till deatha | |||||||||
1 | single rapid transverse rotation | 7 | 250 (± 10) | 116.70 (± 21.18) b | + (+) | + | 4.5–8.7 axons/ mm2 | ||
2 | control | 1 | 0 | 0 | - (−) | – | – | ||
Raghupathi 2004 [7]: 11 piglets + 3 controls; 3-to-5-day-old, 6 h till death a | |||||||||
1 | single transverse rotation | 5 | 172 (± 17) | 50.84 (± 5.56) c | 60% (−) | – | 80% | ||
2 | double transverse rotation, 10–15 ms apart | 6 | 136 (± 8) and 140 (± 6) | 34.38 (± 8.88) and 35.98 (± 7.03) c | 100% (−) | – | 83.3% | ||
3 | controls | 3 | 0 | 0 | - (−) | – | – | ||
Friess 2007 [8]: 18 piglets + 9 controls; 3-to-5-day-old, 12 days till death | |||||||||
1 | single moderate transverse acceleration 188 rad/s | 10 (3 excl) | 188 (± 7) | 62.90 (± 10.1) | - (100%) | 10% | 50% | ||
2 | controls moderate group | 5 | - (−) | – | – | ||||
3 | 2 consecutive rapid transverse acceleration 142 rad/s, ± 3.1 min apart (mild) | 8 | 142 (± 2) | 34.12 (± 28.0) | - (−) | – | – | ||
4 | controls mild group | 4 | 0 | 0 | - (−) | – | – | ||
Friess 2009 [9]: 21 piglets + 7 controls; 3-to-5-day-old, 5 days or 12 days till death | |||||||||
1 | single transverse injury, 12 d survival | 7 (3 excl) | 193.7 | 58.51 | 1 severe, 1 moderate | 0.07% (2 brain stem) | |||
2 | double transverse injury 1 d apart, 12 d survival | 7 (3 excl) | 196.7 and 195.9 | 55.17 and 54.35 | 2 severe | 0.36% (3 brain stem) | |||
3 | double transverse 7 d apart, 5 d survival | 7 (1 excl) | 190.3 and 187.6 | 57.32 and 56.14 | 0.37% (1 brain stem) | ||||
4 | controls, 12 d survival | 7 | 0 | 0 | 1 moderate | – | |||
5 | single transverse injury controls, 5 d survival | 5 | 192 (± 1) | 52.55 (± 1.74) | 0.25% total brain (p < 0.03 vs group 1) | ||||
Naim 2010 [10]: 40 piglets + 10 controls; 3-to-5-day-old, 6 days till deathd | |||||||||
2 | single transverse injury + daily intraperitoneal saline injection (IS) | 8 | 194.25 (± 8.11) | 0.18% (p < 0.02) | |||||
4 | uninjured + daily saline injection (US) | 7 | 0 | 0.003% (p = 0.003) | |||||
5 | controls | 10 | 0 | ||||||
Ibrahim 2010 [11]: 10 piglets + 2–3 controls; 4-week-old, 6 h till death a | |||||||||
1 | controls | 2–3? | 0 | 0 | |||||
2 | single transverse injury, low rate | 4 | 128.5 (± 12.6) | 31.6 (± 4.7) | |||||
3 | single transverse injury, moderate rate | 6 | 194.0 (± 14.8) | 61.0 (± 7.5) | P < 0.05 more than controls or low group | P < 0.05 more vs low group or controls | P < 0.05 more than control or low group | ||
Coats 2010 [12]: 51 piglets + 5 controls; 3-to-5-day-old, 6 h till death | |||||||||
1 | single sagittal injury | 13 | 185 (± 17) | 30.6–101 | 100% bilateral | 57% | x | 71% diffuse, 14% focal | |
2 | single coronal injury | 7 | 208 (± 11) | 30.6–101 | 0% bilateral, 71% unilateral | 0% | 0% diffuse, 20% focal | ||
3 | single transverse injury | 31 | 207 (± 31) | 30.6–101 | 96% bilateral | 58% | 53% diffuse, 32% focal | ||
4 | controls | 5 | 0 | 0 | – | – | – | ||
1–3 | overall results | 83% bilateral, 11% unilateral | 48% | ||||||
Eucker 2011 [13]: 29 piglets + 4 controls; 3-to-5-day-old, 6 h till death a | |||||||||
1 | single horizontal (transverse) high velocity | 9 | 198 (± 12) | (100%e) | 56% | 100%e | |||
2 | single coronal injury | 7 | 208 (± 11) | 29% | 0% | 14% | |||
3a | single sagittal injury | 6 | 166 (± 3) | (100%e) | 83%e | 100%e | |||
3b | single horizontal (transverse) low velocity | 7 | 168 (± 3) | (83%e) | 33% | 100%e | |||
4 | controls | 4 | 0 | (0%) | 0% | 25% | |||
Coats 2017 [14]: 50 piglets + 4 controls; 3-to-5-day-old, 6 h, 24 h or 6 days till death f,g | |||||||||
A | sagittal episodic 6 h survival | 5 | 22.96 (± 2.61) | 606.21 (± 160.3) | 20% (SDH + SAH) | 0% | |||
B | sagittal 30 s continuous 6 h survival | 6 | 22.51 (± 4.33) | 606.21 (± 160.3) | 33% (SDH + SAH) | 17% | |||
B | transverse 30 s continuous 6 h survival | 2 | 28.52 (± 4.05) | 780.08 (± 118.03) | 0% (SDH + SAH) | 0% | |||
C | transverse 10 s continuous 24 h survival | 4 | 30.86 (± 0.77) | 780.08 (± 118.03) | 50% (SDH + SAH) | 100% | |||
D | transverse 30 s continuous 24 h survival | 8 | 28.54 (± 2.67) | 780.08 (± 118.03) | 50% (SDH + SAH) | 25% | |||
E | transverse double continuous 24 h survival | 9 | 28.75 (± 3.02) | 780.08 (± 118.03) | 67% (SDH + SAH) | 56% | |||
F | transverse 30 s continuous 6 d survival | 5 | 28.41 (± 3.87) | 780.08 (± 118.03) | 40% (SDH + SAH) | 80% | |||
G | sagittal noncyclic 6 h survival | 5 | 32.19 (± 7.04) | 2857.40 (± 1682.91) | 0% (SDH + SAH) | 0% | |||
H | sagittal noncyclic 24 h survival | 6 | 42.86 (± 6.45) | 866.33 (± 213.92) | 0% (SDH + SAH) | 33% | |||
Sham | controls 6 h and 24 h survival | 2 / 2 | 0 | 0% (SDH + SAH) | 0% |