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Modeling of inflicted head injury by shaking trauma in children: what can we learn?: Part I: A systematic review of animal models


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Inflicted blunt force trauma and/or repetitive acceleration-deceleration trauma in infants can cause brain injury. Yet, the exact pathophysiologic mechanism with its associated thresholds remains unclear. In this systematic review an overview of animal models for shaking trauma and their findings on tissue damage will be provided. A systematic review was performed in MEDLINE and Scopus for articles on the simulation of inflicted head injury in animals. After collection, the studies were independently screened by two researchers for title, abstract, and finally full text and on methodological quality. A total of 12 articles were included after full-text screening. Three articles were based on a single study population of 13 lambs, by one research group. The other 9 articles were separate studies in piglets, all by a single second research group. The lamb articles give some information on tissue damage after inflicted head injury. The piglet studies only provide information on consequences of a single plane rotational movement. Generally, with increasing age and weight, there was a decrease of axonal injury and death. Future studies should focus on every single step in the process of a free movement in all directions, resembling human infant shaking. In part II of this systematic review biomechanical models will be evaluated.
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Modeling of inflicted head injury by shaking trauma in children: what
can we learn?
Part I: A systematic review of animal models
Marloes E. M. Vester
&Rob A. C. Bilo
&Arjo J. Loeve
&Rick R. van Rijn
&Jan Peter van Zandwijk
Accepted: 1 January 2019
#The Author(s) 2019
Inflicted blunt force trauma and/or repetitive acceleration-deceleration trauma in infants can cause brain injury. Yet, the exact
pathophysiologic mechanism with its associated thresholds remains unclear. In this systematic review an overview of animal models
for shaking trauma and their findings on tissue damage will be provided. A systematic review was performed in MEDLINE and
Scopus for articles on the simulation of inflicted head injury in animals. After collection, the studies were independently screened by
two researchers for title, abstract, and finally full text and on methodological quality. A total of 12 articles were included after full-
text screening. Three articles were based on a single study population of 13 lambs, by one research group. The other 9 articles were
separate studies in piglets, all by a single second research group. The lamb articles give some information on tissue damage after
inflicted head injury. The piglet studies only provide information on consequences of a single plane rotational movement. Generally,
with increasing age and weight, there was a decrease of axonal injury and death. Future studies should focus on every single step in
the process of a free movement in all directions, resembling human infant shaking. In part II of this systematic review biomechanical
models will be evaluated.
Keywords Closed head injuries .Child abuse .Forensic pathology .Animal models
Head injury in young children (under the age of 5 years) can be
caused by several mechanisms, such as compression/crushing,
blunt force, repetitive acceleration-deceleration, and penetra-
tion. These mechanisms may lead to injuries to the skin and/
or skull and/or intracranial contents. The circumstances under
which these mechanisms arise can be accidental (e.g. traffic
accidents or falls from height) or inflicted (e.g. child abuse).
The most prevalent causes of inflicted head injury in children
are blunt force (IHI-BFT: inflicted head injury by blunt force
trauma) and repetitive acceleration-deceleration/shaking (IHI-
ST: inflicted head injury by shaking trauma) [1]. In the Western
world the incidence of inflicted head injury is estimated to be
2040 per 100.000 children under the age of 1 year and de-
creases with increasing age [28]. In literature, inflicted head
injury in children has been referred to by many different terms
(Table 1). Most of these terms are suggestive and imply a trau-
ma mechanism or a certain intention. Therefore these terms
should be avoided in a forensic context.
Blunt force has never been the subject of much debate as a
causative mechanism in inflicted head injury. Shaking still seems
to be the subject of an ongoing debate, especially in courts,
despite reliable medical and biomechanical scientific evidence
Marloes E. M. Vester and Rob A. C. Bilo contributed equally to this work.
*Marloes E. M. Vester
Academic Medical Center Amsterdam, Department of Radiology
and Nuclear Medicine, Amsterdam UMC, University of Amsterdam,
Room G1-231, Meibergdreef 9,
1105AZ Amsterdam, The Netherlands
Specialist Services and Expertise Division, Netherlands Forensic
Institute, Laan van Ypenburg 6, 2497 GB The
Hague, The Netherlands
Department of BioMechanical Engineering, Delft University of
Technology, Mekelweg 2, 2628 CD Delft, The Netherlands
Division of Digital and Biometric Traces, Netherlands Forensic
Institute, Laan van Ypenburg 6, 2497 GB The
Hague, The Netherlands
Forensic Science, Medicine and Pathology
that violent shaking can cause severe head injuries. This ongoing
debate is caused by the fact that shakingas cause of inflicted
head injury (IHI) is a conclusion that is mainly based on exclu-
sion of other causes (medical conditions, birth trauma, and acci-
dental trauma after birth), combined with the absence of findings
consistent with blunt force trauma (e.g. bruising of the scalp or a
skull fracture) and confessions of perpetrators. Because the use of
human infants as experimental research population is impossible
due to ethical standards, research is restricted to juvenile animals,
mechanical surrogates, and mathematical models.
The aim of part I of this systematic review is to discuss
juvenile animal studies used to cause intracranial and retinal
injuries after repetitively induced head motions without a direct
impact mechanism. Part II will elaborate on the physical and
mathematical models concerning shaking in young children.
In shaking the acceleration-deceleration forces are
mostly oriented within the sagittal plane (forward-back-
ward), but movements in the transverse (no- shaking of
ones head; around the body axis, also commonly re-
ferred to as axial or horizontal) and coronal (sideways;
ear to shoulder) plane will also occur. Since sagittal
movements are considered to be the main component in
shaking, most of the injury is also believed to be the
result of this motion [9]. In shaking, forces applied onto
the torso (grasping and shaking) are transferred by the
neck to the skull, followed by stresses and strains on the
soft tissues in the skull (Fig. 1). When stress and strain
exceed certain thresholds, material failure of the tissue
(injury) will occur, such as retinal hemorrhages, rupture
of bridging veins leading to subdural hemorrhages
(SDH), and post-traumatic encephalopathy (i.e. diffuse
axonal injury; DAI). These physiological transference of
forces will be discussed in more detail in Part II of this
systematic review. Conclusive data on the exact patho-
physiology and threshold values needed to cause these
injuries in cases where IHI-ST is suspected has not been
reported in the literature. The purpose of this review is to
identify animal models specific for shaking trauma and
their findings concerning tissue damage.
Database search
MEDLINE (Pubmed) and Scopus® were systematically
searched up to January 1st, 2017. Five search queries were
built, using both free terms and indexed terms for mechanical
models, mathematical models, and animal models that mimic
IHI-ST (Appendix). Articles in Dutch, English, French, and
German were included.
Article selection
Identified articles were de-duplicated in Endnote and
subsequently divided into the three (physical, mathemat-
ical, and animal) study models. Two researchers (RR and
MV) each assessed all articles in the animal subgroup on
title, abstract, and lastly on full text, based on relevance
for the understanding or explanation of (aspects of) IHI-
ST pathophysiology. In case of disagreement, a third re-
searcher (RB) was consulted. Manual reference
snowballing of the included articles was performed by
RR and MV. The main authors of the included articles
were contacted for additional, possibly unpublished stud-
ies and information.
All prospective animal studies on the biomechanics of IHI-
ST were included. Exclusion criteria were direct (blunt force)
trauma to the head, non-objective studies (observational stud-
ies of animal behavior), or adult animals (because of incom-
parable development of the nervous system, matured muscle
strength and weight). Full-texts were assessed on the method-
ological quality using a standardized form adapted from the
Critical Appraisal Skills Program (CASP) (available upon
Table 1 Inflicted head injury by
shaking trauma in children:
synonyms in the medical
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
Forensic Sci Med Pathol
request) [10]. In case of doubt on the methodological quality
or study design, the main authors were contacted for addition-
al information.
Data extraction
Data extraction was performed by authors MV and RB using a
predefined data-extraction form (available upon request).
Baseline features such as study design and animal characteris-
tics (e.g. age, gender) were recorded. Furthermore, trauma
mechanism, measurement of inflicted forces and accelerations,
cerebral macroscopy and microscopy, ophthalmological results,
and the main interpretations and conclusions were extracted.
Search results & quality assessment
The initial search resulted in a total of 4675 articles, of which
1977 eligible articles remained after deduplication (Fig. 2).
1954 articles were excluded based on title or abstract, leaving
23 articles for full-text assessment. Thirteen articles about IHI-
ST were excluded based on no IHI-ST, absence of
neuropathophysiological results, or inadequate methodologi-
cal reporting [1118]. Therefore, ten articles remained after
full-text assessment, and two additional articles were identi-
fied by snowballing. The remaining 12 articles, three in lambs
and nine in piglets, were published by two research groups.
The two main researchers of these groups (JW Finnie and S
Margulies) were contacted for additional information. The
three articles on lambs originated from a single study, whereas
the nine piglet studies were all individual studies. All studies
were small, prospective studies of low quality as assessed by
Studies in lambs
The Finnie-group published three articles on a single study
design [9,19,20]. Table 2provides extensive study details.
The overall design included nine injuredand four control
lambs, 5-to-10-days-old. The free shakingmechanism ap-
plied by humans on the lambs in this study design, closely
resembled shaking in human babies, according to the authors.
Manual shaking of lambs caused extra-axial hemorrhages in
both younger lambs(56 kg) and older lambs(8.512 kg)
(Table 2). Injuredanimals had significantly more β-APP
positive neuronal perikaryons, equal in both age groups.
Fig. 1 The 7-step description of inflicted head injury by shaking in children
Forensic Sci Med Pathol
Nevertheless, total injury scores and cranio-cervical junction
related injury (region of maximal impact loading), hypoxic
edema without ischemia, and C-fos immunoreactivity were
higher in the younger lambscompared to the older lambs
in the publications of 2012 and 2013 (Table 2)[19,20]. None
of the spinal cords showed parenchymal hemorrhages or
hypoxic-ischemic damage. The first published article in
2010 did not report on the three younger lambs, which all
died before the designated survival time of 6 h post-injury,
with signs of Axonal injury (AI), neuronal reaction, and albu-
min extravasation [20].
Injuredlambs, more commonly the younger ones,
showed damage of the retina with increased GFAP, multifocal
damage of the inner nuclear layer neurons, mild segmental
splitting, and increased β-APP expression [19,20].
Additionally, there was albumin extravasation in the uvea.
Minor retinal hemorrhages were, amongst others, seen in both
of the older lambswith a SDH [9].
Overall, the injuredlambs showed injuries of the brain,
spinal cord, and eyes, while the control animals did not show
any relevant abnormalities. Injury was more common and
more extensive in the lower weight, younger lambs, which
all died prematurely.
Studies in piglets
The Margulies-group published nine articles, all of individual
studies with 3-to-5-day-old piglets, apart from the 4-week-old
piglets of Ibrahim et al. [2129]. See Tables 3,4,and5for
more extensive details of the respective articles. Naim et al.
injected half of their tested piglets with folic acid, which is
beyond the scope of this review and data pertaining tothat part
of the study will hence not be included in this review [25]. In
all pig studies, the animals were secured to a bite plate or
padded snout clamp and moved in a single plane (Fig. 3).
All but Coats et al. [27,29] and Eucker et al. [28], rotated
Fig. 2 Prisma flowchart for the
conducted literature search and
article selection process of animal
inflicted head injury by shaking.
Numbers in the flowchart
following the +sign are articles
identified through snowballing
Forensic Sci Med Pathol
solely in the transverse (also referred to as axial) plane
(Table 5)[2126]. Head movements were applied as single,
consecutive/double-single, or continuously repeated rotations.
Macroscopy and microscopy (HE-staining, β-APP, NF68,
NF200, and/or avidin-biotinperoxidase (ABC) histochemis-
try) was performed in all studies, although not on all brains.
Furthermore, cervical spinal cords were examined by some,
No unintended mortality or morbidity was described in five
of the nine piglet articles (Tables 3,4,and5)[21,22,2629].
Friess et al. did not find mortality either but excluded 3 piglets
from their moderate accelerationgroup (62.9 krad/s
ate fractures and 1 with inability to feed), see Table 3[23]. A
significantly higher mortality (43%) was reported by Friess
et al. for the double rotation, 1-day apart group (average
55.2 and 54.3 krad/s
for respectively the first and second
rotation) (1 apnea, 1 poor neurological outcome, and 1 un-
known), compared to animals in which a single rotation was
applied (average 58.5 krad/s
come, p< 0.05) (Table 3)[24]. Three additional animals were
sacrificed because of palate fractures (2 from the single rota-
tiongroup, 1 from the 1-week apartgroup). In the study of
Naim et al. 7 injured piglets died: 2 of hard palate fractures, 1
apnoea/cervical spine hematoma, and 3 large SDHs [25].
Duration of unconsciousness was reported in four articles.
Raghupathi et al. did not find overt or extensive loss of con-
sciousness in their injured piglets [21]. Their double rotation,
1-day apart group (average 55.2 krad/s
and 54.3 krad/s
respectively the first and second rotation) (Table 3) had sig-
nificantly longer unconsciousness durations than controls on
day 0 (10.1 ± 3.4 SD vs. 2.8 ± 0.7 SD min) in the study of
Friess et al. [24]. On day 7, the 1-week apart group (average
57.3 and 56.1 krad/s
for respectively the first and second
rotation) also had significant longer unconsciousness dura-
tions than controls (5.1 ± 0.7 SD vs. 2.8 ± 0.7 SD min). In
the study of Naim et al. (Table 3) unconsciousness durations
were significantly longer in the injured group (6.27 ± 0.1 SD
min) compared to the control group (3.58 ± 0.1 SD min; p=
0.01) [25]. Furthermore, all piglets with a moderate-
acceleration (average 61.0 krad/s
) injury of Ibrahim et al.
were apneic post-injury, compared to 50% of the low-
accelerated animals (average 31.6 krad/s
) and 0% of controls
(p< 0.05) (Table 4)[26].
Ocular examinations were reported on by Coats et al.
[27,29]. In the 51 injured piglets (average 30.6 krad/s
ied by Coats et al. in 2010 [27] ocular hemorrhages were
found in 73% of these 51 piglets, of which 51% were bilateral
and primarily located near the vitreous base. In cases with
bilateral SDHs 26 (68%) had ocular hemorrhages, compared
to one in a unilateral SDH case. All but two animals with
ocular hemorrhages had brain injury. In their study from
2017Coats et al. [29] found no ocular injuries at all, possibly
explained by a five-times lower rotational velocity compared
to other studies e.g. Coats et al. 2010 [27](Table5).
Friess et al. [24] and Naim et al. [25]didnotreportany
axial or extra-axial hemorrhages, which were reported in all
other studies (Table 6). In general, hemorrhages are more fre-
quent and more severe with increasing force, duration, or rep-
etition. Coronal rotations had less frequent, and less severe
hemorrhages and axonal injury (AI) at microscopy in Coats
Table 2 The single study design used for the three articles by Finnie et al. 2010, 2012, and 2013 [13]
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 (512)
9 lambs + 4 controls (2012 and 2013 articles) [2,3]
- Age matched 7- to-10-day-old, 8.7 kg (512)group1(n=6):older, 10.3 kg [8.512 kg]
- Age matched 7- to-10-day-old, 8.7 kg (512)group2(n=3):younger,5.5kg[56kg]
- Age matched 7- to-10-day-old, 8.7 kg (512)controls (n= 4): 7- to-10-day-old, [510.5 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 (overnightin 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 Published by Sandoz et al. 2012 and Anderson et al. 2014 [4,5]: shaking by human subjects was applied
with a frequency of about 2 Hz, thus ±40 cycles/episode. Resulting accelerations were between 40 and 80 g,
with an average peak acceleration of 62 g.
β-APP immunohistochemistry: (upregulation indicates differentiation of neurons after injury), C-fos and EMA (epithelial membrane antigen): indication
of neuronal activity. HE-stain hematoxylin and eosin stain
Forensic Sci Med Pathol
Table 3 Study design of piglet articles with shaking solely in a transverse plane (often referred to as axial in the articles) [610]
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 (1.53.0, 3
unknown). Average brain
weight: 35 g (3338).
Anesthesia and ventilation.
Rapid, inertial,
non-impact, transverse
head rotation 110° over
1012 ms, centered in
the cervical spine, with
HYGE pneumatic
actuator. Heads secured
to padded snout clamp.
68 h anesthesia and
ventilation before death.
Heparin perfusion, in situ
fixation with 10%
formalin, followed by
ex-situ fixation
Macroscopy and
microscopy of brain,
cerebrum, and brain
stem with Nissl staining,
NF68 and NF200
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
11 piglets + 3 controls;
3-to-5-day-old. Group 1
(n= 5): single rotation
(15 ms), ± weight 2.0 kg
(1.82.4), ± brain weight
36 g. Group 2 (n=6):
double rotation (15 ms,
1015 m apart), ± weight
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
Macroscopy and
microscopy of brain,
cerebrum, and brain
stem with NF200
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
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, 13 min after
end of isoflurane. Heads
After 12 days
re-anesthetized, death by
pentobarbital, heparin
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
and counterstained with
Meyers hematoxylin.
Moderate acceleration:
62.90 ± 10.10 krad/s
velocity: 188 ± 7 rad/s.
Mild acceleration:
34.12 ± 2.80 krad/s
velocity: 142 ± 2 rad/s.
Friess 2009 [9]
Journal of Neurotrauma
Repeated traumatic brain
injury affects composite
cognitive function in
To develop a cognitive
composite dysfunction
score to correlate white
matter injury severity in
piglets with
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 1012 ms
with HYGE pneumatic
actuator. Heads secured
to padded bite plate.
After 12 days
re-anesthetised, death by
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
Meyers hematoxylin.
Velocity: Gr 1::
193.7 rad/s, Gr 2:
196.7195.9 rad/s, Gr
3:: 190.3187.6 rad/s
Acceleration: Gr 1: 58.51
55.1754.35 krad/s
Gr 3: 57.3256.12
Naim 2010 [10] To test if folic acid
supplementation after
4 groups: 40 female + 10
male piglets,
Anesthesia and ventilation.
Rapid, inertial, 90110°
After 6 days
re-anesthetized, death by
Behavioral testing on days
1 and 4 following injury.
Angular velocity:
Forensic Sci Med Pathol
Tab l e 3 (continued)
Article Objective Animals Trauma mechanism Fixation Outcome measures Input dynamics
Folic Acid Enhances Early
Functional Recovery in a
Piglet Model of Pediatric
Head Injury
injury would decrease
the severity of TAI in our
well-established piglet
model of moderate
pediatric head injury.
3-to-5-day-old. Group 1
(n= 7): injured + daily
intraperitoneal folic acid
injection (IF) 2.24 kg.
Group2(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
transverse rotation,
spine with the HYGE
pneumatic actuator.
Heads secured to padded
bite plate.
pentobarbital, heparin
with 10% formalin.
Macroscopy and
microscopy of brain,
cerebrum, brain stem,
and high cervical spinal
cord with HE staining,
β-APP staining, and
counterstained with
Meyers hematoxylin.
IF group:
193.29 ± 5.31 rad/s,
IS group:
194.25 ± 8.11 rad/s
β-APP immunohistochemistry (β-amyloid precursor protein) HE-stain hematoxylin and eosin stain, NF Neurofilament ABC avidin-biotinperoxidase histochemistry, PAV peak angular velocity
Table 4 Study design of 4-week old piglet article [11]
Article Objective Animals Trauma mechanism Fixation Outcome measures Input dynamics
Ibrahim 2010 [11]
Journal of
Physiological and
responses to head
rotations in toddler
To characterize the
physiological and
pathological responses
of the immature brain to
inertial forces and their
relationship to
13 female piglets; brain weight
56.04 g, 4-week-old.
Group 1 (n= 2): controls,
Group 2 (n=4):lowrate
angular acceleration, Group 3
(n= 6): moderate rate angular
Anesthesia and ventilation.
Single non-impact,
transverse rotation,
centered in the cervical
spine. Heads secured to
padded bite plate with
snout straps and pneumatic
Euthanized 6 h after
injury. Death by
pentobarbital, in situ
perfusion fixation
with 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
Acceleration: low
(31.6 ± 4.7 krad/s
,) or
moderate (61.0 ± 7.5
,). PAV: low:
129 ± 13 rad/s, moderate
194 ± 15 rad/s.
β-APP β-amyloid precursor protein, HE-stain hematoxylin and eosin stain, NF Neurofilament, PAV peak angular velocity
Forensic Sci Med Pathol
Table 5 Study design of piglet articles with movement in multiple planes [1214]
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
6 h anesthesia before death
by heparin infusion and in
situ fixation with 10%
formalin. Ex situ fixed
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
117266 rad/s and
30.6101 krad/s
Eucker 2011 [13]
Experimental Neurology
Physiological and
responses following
closed rotational head
injury depend on direction
of head motion
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):
Anesthesia and ventilation. A
single rapid (1220 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 Meyers 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]
Cyclic Head Rotations
Produce Modest Brain
Injury in Infant Piglets
To systematically
investigate the
pathological time
course after cyclic
low-velocity head
rotations and compare
them with single head
50 piglets + 4 controls;
3-to-5-day-old. Group A
(n= 5): sagittal, episodic.
Group B (n= 6 sagitt al, 2
transverse): continuous 30 s.
Group C (n= 4): t ransverse,
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)24h
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
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; 23Hz.
Sagittal: peak-to-peak
average angular velocity
(unclear how this was
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.
β-APP β-amyloid precursor protein, HE-stain hematoxylin and eosin stain, NF Neurofilament, PAV peak angular velocity
Forensic Sci Med Pathol
et al. and Eucker et al. compared to sagittal or transverse
rotations (Table 6)[27,28]. Eucker found a significantly
higher subarachnoid hemorrhage (SAH) score for high veloc-
ity, transverse (in the article referred to as horizontally) rotated
piglets and sagittal rotated piglets comparedto controls. Extra-
axial hemorrhages were mainly located frontally in the
Raghupathi articles [21,22].
The time between two injuries and the time between injury
and measurement might be of influence on the extent of mea-
sured AI, according to Friess et al. and Coats et al. [24,29].
Single rotated piglets surviving 12 days (average 58.5 krad/s
had significantly less β-APP staining (sign of AI: 2 h to 4
6 weeks) compared to single rotated piglets surviving 5 days
(p< 0.03), thus less white matter injury was detected over time
[24]. Episodic and continuous cyclic head rotations for 30 s
had no differences in the amount of AI after 6 h [29]. There
was a significant increase in AI with increasing post-injury
time (24 h vs. 6 h) for 30 s continuous rotated animals (p=
No AI was found in the controls. AI was found in all stud-
ies to some extent in injured groups, although not always
significantly different from the control groups. Raghupathi
et al. found no neuronal loss, nor a relation between the ve-
locity and density of AI located in multiple white matter tracts
[21]. In 2004 they reported that two consecutive rotations
caused AI in the peripheral subcortical and central deep white
matter regions, especially more foci with multiple injured
axons (p= 0.05) compared to a single rotation [22]. After a
single rotation, AI was found in the peripheral subcortical and
central deep white matter regions in the frontal lobes. After
two consecutive rotations, AI was also present in the white
matter of the parietal and temporal lobes, corpus callosum,
hippocampus, and basal ganglia. Friess et al. found AI in the
olfactory tract, germinal matrix, internal capsule, and some
posteriorly in the moderately rotated piglets (average 62.9
), compared to no AI in the mildly rotated group (av-
erage 34.1 krad/s
)(Tables3and 6)[23]. In 2009 they report-
ed that the majority of AI was located in the frontal lobes in
injured animals with a significantly greater white matter β-
APP injury volume in all three injury groups compared to
uninjured animals [24]. Naim et al. found white matterinjuries
mostly in the deep white matter of the frontal lobes and some
in parietal and temporal lobes or brainstem [25]. Eucker et al.
found a significantly greater early ischemia score in the sagit-
tal rotations than in controls [28]. High velocity transverse
rotations resulted in significantly more AI than coronal or
low-velocity horizontal rotations (Table 5). Both sagittal and
transverse rotations produced the greatest degrees of tissue
pathology, whereas coronal rotations did not result in any
significant pathology. AI was more extensive in the anterior
regions of the brain compared to other brain regions for every
injury group, after multiple regression analysis. Coats et al.
found injury in 88.5% of the cyclic rotated animals surviving
24hand6days[29]. After 24 h there were significantly more
animals with AI after continuous rotations for 10 s than 30 s
(p= 0.014). There was more hypoxic-ischemic injury and
extra-axial hemorrhages in 30 s continuous rotated piglets
than in piglets with a single head rotation, but this was only
noticeable after 24 h.
Ibrahim et al. compared the result of 4-week-old piglets to
the previously published results by Eucker et al. in 5-day-old
piglets [26,30]. They found no significant differences in SAH
scores and brain volume of AI between those two groups.
However, when comparing these 4-week-old animals to 5-
day-old piglets, based on the mass scaled acceleration princi-
ple of Ommaya and Hirsch, 1971 [31], there was a significant
difference for both SAH scores (p< 0.02) and brain volume of
AI (p< 0.004). In comparison to lower rotational acceleration
(average 31.6 krad/s
), larger rotational accelerations (average
61.0 krad/s
) caused more severe SAH, more areas of ische-
mia, and larger volumes of AI.
Ommaya was the first to describe brain injury after a whiplash
trauma in primates with SDH in 15 out of 19 monkeys with a
concussion [14,32,33]. IHI-ST is, as stated before, still an
Fig. 3 Rotational planes in animal studies of IHI-ST
Forensic Sci Med Pathol
Table 6 Outcomes in piglet studies [614]
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)
Raghupathi 2002 [6]: 7 piglets + 1 control; 3-to-5-day-old, 68 h till death
1 single rapid transverse rotation 7 250 (± 10) 116.70 (± 21.18)
+(+) + 4.58.7 axons/ mm
2 control 1 0 0 - ()––
Raghupathi 2004 [7]: 11 piglets + 3 controls; 3-to-5-day-old, 6 h till death
1 single transverse rotation 5 172 (± 17) 50.84 (± 5.56)
60% ()80%
2 double transverse rotation, 1015 ms apart 6 136 (± 8) and
140 (± 6)
34.38 (± 8.88) and
35.98 (± 7.03)
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
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 death
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 + 23 controls; 4-week-old, 6 h till death
1 controls 23? 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<0.05more than
controls or low group
P< 0.05 more vs low
group or controls
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) 30.6101 100% bilateral 57% x 71% diffuse, 14% focal
2 single coronal injury 7 208 (± 11) 30.6101 0% bilateral, 71%
0% 0% diffuse, 20% focal
Forensic Sci Med Pathol
Tab l e 6 (continued)
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)
3 single transverse injury 31 207 (± 31) 30.6101 96% bilateral 58% 53% diffuse, 32% focal
4 controls 5 0 0 –– –
13 overall results 83% bilateral, 11%
Eucker 2011 [13]: 29 piglets + 4 controls; 3-to-5-day-old, 6 h till death
1 single horizontal (transverse) high velocity 9 198 (± 12) (100%
) 56% 100%
2 single coronal injury 7 208 (± 11) 29% 0% 14%
3a single sagittal injury 6 166 (± 3) (100%
) 83%
3b single horizontal (transverse) low velocity 7 168 (± 3) (83%
) 33% 100%
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
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%
SDH subdural hematoma, SAH subarachnoid hemorrhage, PH parenchyma hemorrhage, AI axonal injury
peak angular velocities instead of angular velocities,
deceleration instead of acceleration,
maximal deceleration instead of acceleration,
Because of intervention piglets injected with folic acid are not
representable for IIHI in human infants, and thus excluded from this table,
peak-to-peak angular velocities,
angular acceleration in rad/s
instead of krad/s
. NB: not all brains were
macroscopically and/or microscopically examined
Forensic Sci Med Pathol
important and current topic of debate. It might be expected
that this would be reason for extensive studies in animals in
the past by many different research groups. However, in this
systematic review, only two research groups had usable arti-
cles. Older articles from 1998, 2002, and 2004 in rodents were
excluded for their inconclusive reporting of methodology and
results [12,13,16,17]. Though Ommaya was the first to
describe these kinds of injuries, the used trauma mechanism
is incomparable to that of IHI-ST, why these studies were also
excluded. The included piglet and lamb articles are difficult to
compare because of differences in species, age, trauma mech-
anisms, and small study groups without source data available.
With increasing moral and ethical standards, animals are less
and less used as study objects and replaced by mathematical
and physical models as described in Part II of this review.
These two combined systematic reviews are the novel for
IHI-ST, as described earlier, is most closely resembled by the
study with shaken lambs. Like in human babies, the lambs
were held by adults around the ribcage leaving the head free
for acceleration-deceleration rotation in any direction for a
significant amount of time (30 s) without a direct impact trau-
ma. Accelerations generated in lambs by shaking have been
reported by Sandoz et al. and Anderson et al. [11,15].
Although the articles state that the lambs were shaken for
20 s, additional information by the main author confirmed that
the shaking was actually for 30 s as in the three Finnie articles.
Anderson added that three adults manually shook the animals,
mainly in the sagittal plane. Shaking speed and perimeter dif-
fered per person and weight of the animals. Forces were mea-
sured with a triaxial piezoresistive accelerometer (8 g,
2000 Hz, model 7268C, Endevco©) and a motion tracking
sensor (9.1 g, 60 Hz, Fastrak-Polhemus©) on the head and
one motion tracking sensor under the axilla. Animals were
shaken with approximately 2 Hz, thus around 40 cycles per
shaking episode [11]. Accelerations (in absolute value, not
cases, with a maximum of 26.64 g [15]. Acceleration of im-
pulses >30 g had peak measurements of 58-79 g and average
peak accelerations of 35.941.6 g for the younger animals,
and 39-80 g and 34.144.9 g, respectively, for the older lambs.
The lambs were compared to 9-month-old human infants
by the authors, based on their body weight. The pathophysi-
ology of trauma due to shaking was deemed comparable to
human infants since both have weak neck muscles, though
this effect might have been exaggerated by the anesthesia in
the lambs. Both human infants and lambs have a relatively
large head/brain compared to the body, along with a wide
subarachnoid space, allowing a relatively large brain move-
ment within the skull [34]. Both have brains that are not yet
fully myelinated, with a higher brain water content, and there-
by an increased vulnerability to shearing injury [9,35]. This
may explain the more extensive injuries in the younger lambs
compared to the older lambs (Table 2). The lamb brain is more
elliptically shaped and is in line with the myelum and cervical
spinal cord compared to an almost 90-degree angle between
the rounder human brain and the spinal cord. The effect of the
difference in shape and orientation of the brain is not known.
A drawback of these publications on lambs is the fact that,
according to the main author, all three articles were based on
the same nine injured and four control lambs. Results there-
fore should be reproduced by other and larger studies.
In all piglet studies, except Coats et al. [29], only single ac-
celerations were applied to the study animals. This reduces its
value for translation to human shaken babies as it is believed
by many that the repeated sudden deceleration, in combination
with the acceleration, causes the intracranial injury [34].
When shaking a human baby, the head will rotate mostly in
a sagittal plane, but may sustain rotations in the transverse and
coronal planes, along with possible chin-chest collisions, de-
pending on body weight and individual shakers [11].
Inconsistency in the use of terminology for rotation directions
hinders interpretation and translation to humans. Different ro-
tation planes have been studied by Coats et al., Eucker et al.,
and Coats et al. [2729]. However, none of these studies com-
bined the different rotation planes, while simultaneously oc-
curring rotations in different directions might amplify the
forces and deformations exerted on the anatomical structures
in the head and hence worsen the resulting injuries.
Furthermore, chin-chest collisions were avoided within these
studies. More importantly, the single plane movement (only
transverse in 6 out of 9 piglet studies) thus does not represent
the main repeated back-and-forth motions and internal trans-
lation of forces in IHI-ST. Therefore, there are insufficient data
to estimate whether and to what extent the results of these
studies could be translated to IHI-ST.
Though executed and published by a single research group,
specific reports on physics are inconsistent. Angular velocities
are reported by Friess et al. [23,24], Naim et al. [25] and Coats
et al. [27] compared to peak angular velocities by Raghupathi
et al. [21,22], Ibrahim et al. [26] and Coats et al. [29], and
even peak-to-peak angular velocities by Coats et al. [29].
Where most articles report on angular accelerations,
Raghupathi et al. report on decelerations in 2002 and maxi-
mum decelerations in 2004. Furthermore, most reported an-
gular accelerations were in krad/s
ranges, such as Coats et al.
[27], who reported 30.60101 krad/s
for angular velocities of
177266 rad/s. These high angular velocities do, depending
on the angle over which the head was moved (which is, un-
fortunately, not in all articles reported), resemble shaking with
Forensic Sci Med Pathol
frequencies of 20 to 161 Hz, assuming angular ranges of mo-
tion of 110 to 30 degrees.
Shaking in human infants is often not a onetime occurring
incident in time, but an event reoccurring over longer periods
of time. Friess et al. and Raghupathi et al. postulated that
repeating of the trauma within 24 h might increase the sensi-
tivity to injury by latent readjustment or injury accumulation
[22,24]. Besides the aforementioned influences of anesthesia,
buprenorphine and isoflurane anesthetics used in the piglet
studies might have some neuroprotective features and could
affect the results by reducing the injury [36,37]. Mortality was
reported in none of the articles. Friess et al. excluded some
piglets because e.g. palate fractures or an inability to being fed
due to the injury procedure. Because of exclusion those piglets
were not counted as a mortality [23,24].
Like humans, pigs have a gyrencephalic brain, with similar
grey-white differentiation and physiological responses, and
are therefore commonly used as a model for human infants.
A 3-to-5-day-old piglet brain can be roughly compared to a 2-
to-4-weeks-old human baby based on activity, myelination,
and growth. Ibrahim et al. state that a 4-week-old piglet brain
is comparable to a 2- to-4-year-old human brain based on
development and myelination. Like the lamb brain, the piglet
brain is more elliptically shaped and angled in line with the
myelum and cervical spinal cord, compared to an almost 90-
degree angle between the rounder human brain and the
myelum. The single plane rotational movement in the piglet
studies and the unalike anatomy make the results of these
studies difficult to translate to the human infant.
The piglets eye has more in common with the human eye
than most other animalseyes, for example, the retina vascu-
larization and the vitreous base, although there are also differ-
ences such as the absence of a fovea or macula [38,39]. The
acceleration-deceleration trauma in IHI-STis thought by some
to cause the vitreous body to pull on the retina and conse-
quently induce vascular injury. Yet, due to all the differences,
it is hard to estimate whether the results of Coats et al. [27]
could be used for human injury assessment.
Injury sustained by lambs in shaking studies gives some in-
formation on the relationship between the applied shaking
accelerations, the animal, and the clinical outcome. Older,
heavier lambs had less AI and deaths. For piglets, it was found
that rotation direction influenced the neurological symptoms
and neuropathological findings. Tissue strain might be of in-
fluence on these injuries, yet the anatomical differences and
the inconsistent choice of (mostly noncyclic) rotation direc-
tions in the various studies make an adequate comparison very
difficult. With regard to the ocular results in piglets, no direct
translation to human infants can be made due to differences in
anatomy and a lack of evidence of the relevance of these
differences. The study in 4-week-old piglets might provide
some information about single rotational impacts in toddlers,
but lacks confirmation by other studies. Future studies should
therefore focus on understanding each individual step in the
IHI-ST process and its respective accelerations, forces, tissue
deformations and injury thresholds. Ideally, experimental con-
ditions should allow a free movement of the head in all direc-
tions, without any external impacts, in simulations compara-
ble to inflicted head injury due to shaking in human infants.
Key points
1. Despite the importance for understanding IHI-ST, ade-
quate large randomized animal studies are lacking in the
2. Animal articles, closely representative of IHI-ST as pre-
sumed to occur in human infants, are only available from
a single study in lambs.
3. Studies in piglets provide some information on IHI-ST,
mostly about a fast transverse acceleration, but are other-
wise difficult to translate to human infants because of the
(non-cyclic) rotational movement restrictions.
4. Future research should focus on larger, more consistent
animal studies, validating the applicability of juvenile an-
imal experiments as a model of human IHI-ST.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
Ethical approval and informed consent Not applicable to this system-
atic review.
Appendix 1 Search Queries
Q1. ((finite[All Fields] AND (elements[MeSH Terms] OR
elements[All Fields] OR element[All Fields]) AND
shaken[All Fields]) OR (((biomechanical[All Fields]
AND shaken[All Fields]) OR ((models,
animal[MeSH Terms] OR (models[All Fields]
AND animal[All Fields]) OR animal models[All
Fields] OR (animal[All Fields] AND model[All
Fields]) OR animal model[All Fields]) AND (shaken
baby syndrome[MeSH Terms] OR (shaken[All
Fields] AND baby[All Fields] AND syndrome[All
Fields]) OR shaken baby syndrome[All Fields] OR
(shaken[All Fields] AND baby[All Fields]) OR
shaken baby[All Fields]))) OR (non[All Fields]
AND accidental[All Fields] AND (craniocerebral
trauma[MeSH Terms] OR (craniocerebral[All
Forensic Sci Med Pathol
Fields] AND trauma[All Fields]) OR craniocerebral
trauma[All Fields] OR (head[All Fields] AND
injury[All Fields]) OR head injury[All Fields])
AND model[All Fields]))) OR ((Simulation[Journal]
OR simulation[All Fields]) AND shaken[All Fields])
Q2. (((((((biomechanical) OR animal model) OR finite ele-
ment) OR simulation) OR mannequin) OR dummy))
AND (((shaken baby) OR abusive head trauma) OR
non accidental head)
Q3. (((Biomechanical Phenomena/methods [Mesh]) OR
(((((((biomechanical model) OR biomechanical evalua-
tion) OR biomechanical study) OR biomechanical) OR
biomechanical analysis) OR Models,
Neurological[Mesh]) OR Models,
Theoretical[Mesh]))) AND ((((((((((((Hematomas,
Subdural) OR Subdural Hematomas) OR Subdural
Hematoma) OR Hemorrhage, Subdural) OR
Hemorrhages, Subdural) OR Subdural Hemorrhage)
OR Subdural Hematoma, Traumatic) OR Subdural
Hemorrhages) OR Hematoma, Traumatic Subdural)
OR Hematomas, Traumatic Subdural) OR Traumatic
Subdural Hematoma) OR Traumatic Subdural
Q4. (((biomechanic* OR dynamic* OR kinematic* OR mo-
tion OR force OR impact) AND (phenomena OR meth-
od OR model OR evaluation OR study OR analysis))
OR (finite elementOR FEM)OR((animalORneu-
rological OR theoretical) AND model) OR simulat* OR
doll OR mannequin OR dummy OR anthropomorphic)
AND ((shake* AND (infant OR baby OR impact))
AND (subdural HematomaOR subdural
HemorrhageOR ((craniocerebral OR head OR retinal)
AND (injury OR trauma OR bleeding))) AND ((non
accidentalOR nonaccidentalOR non-accidental)
OR inflict* OR violen* OR abus* OR shaking))
Pubmed was searched using queries Q1 to Q4 and com-
bining their results. Scopus was searched using query Q4.
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distribution, and reproduction in any medium, provided you give appro-
priate credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
Publishersnote Springer Nature remains neutral with regard to jurisdictional
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... The depth of the wound determines the types of management, wound healing potential, and outcome. Its depth is classified into superficial, partial thickness, and full thickness [15]. Superficial wounds are those that affect only the epidermis. ...
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Wound healing is a very dynamic and complex process as it involves the patient, wound-level parameters, as well as biological, environmental, and socioeconomic factors. Its process includes hemostasis, inflammation, proliferation, and remodeling. Evaluation of wound components such as angiogenesis, inflammation, restoration of connective tissue matrix, wound contraction, remodeling, and re-epithelization would detail the healing process. Understanding key mechanisms in the healing process is critical to wound research. Elucidating its healing complexity would enable control and optimize the processes for achieving faster healing, preventing wound complications, and undesired outcomes such as infection, periwound dermatitis and edema, hematomas, dehiscence, maceration, or scarring. Wound assessment is an essential step for selecting an appropriate treatment and evaluating the wound healing process. The use of artificial intelligence (AI) as advanced computer-assisted methods is promising for gaining insights into wound assessment and healing. As AI-based approaches have been explored for various applications in wound care and research, this paper provides an overview of recent studies exploring the application of AI and its technical developments and suitability for accurate wound assessment and prediction of wound healing. Several studies have been done across the globe, especially in North America, Europe, Oceania, and Asia. The results of these studies have shown that AI-based approaches are promising for wound assessment and prediction of wound healing. However, there are still some limitations and challenges that need to be addressed. This paper also discusses the challenges and limitations of AI-based approaches for wound assessment and prediction of wound healing. The paper concludes with a discussion of future research directions and recommendations for the use of AI-based approaches for wound assessment and prediction of wound healing.
... The authors suggested that free movement in all directions simulating human infant shaking is required for future studies. In the review paper, the authors did not include shaking trauma animal models in rodents and claimed an inconclusive report of the methodology and result [83]. ...
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Abusive head trauma (AHT) is a serious traumatic brain injury and the leading cause of death in children younger than 2 years. The development of experimental animal models to simulate clinical AHT cases is challenging. Several animal models have been designed to mimic the pathophysiological and behavioral changes in pediatric AHT, ranging from lissencephalic rodents to gyrencephalic piglets, lambs, and non-human primates. These models can provide helpful information for AHT, but many studies utilizing them lack consistent and rigorous characterization of brain changes and have low reproducibility of the inflicted trauma. Clinical translatability of animal models is also limited due to significant structural differences between developing infant human brains and the brains of animals, and an insufficient ability to mimic the effects of long-term degenerative diseases and to model how secondary injuries impact the development of the brain in children. Nevertheless, animal models can provide clues on biochemical effectors that mediate secondary brain injury after AHT including neuroinflammation, excitotoxicity, reactive oxygen toxicity, axonal damage, and neuronal death. They also allow for investigation of the interdependency of injured neurons and analysis of the cell types involved in neuronal degeneration and malfunction. This review first focuses on the clinical challenges in diagnosing AHT and describes various biomarkers in clinical AHT cases. Then typical preclinical biomarkers such as microglia and astrocytes, reactive oxygen species, and activated N-methyl-D-aspartate receptors in AHT are described, and the value and limitations of animal models in preclinical drug discovery for AHT are discussed.
... Published studies of AHT have often been criticized for their case selection bias, and systematic reviews have concluded that there is insufficient scientific, evidence-based research to assess the diagnostic accuracy of the "triad" in positively diagnosing AHT [11][12][13][14][15][16] and controversy exists whether the triad can be produced by shaking alone. Moreover, a diagnosis of AHT is often hampered because a convincing history of the circumstances surrounding a suspected case of AHT is lacking, due to obfuscation by the alleged perpetrator, and there is no reliable witness. ...
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Background Abusive head trauma (AHT), previously known as the shaken baby syndrome, is a severe and potentially fatal form of traumatic brain injury in infant children who have been shaken, and sometimes also sustained an additional head impact. The clinical and autopsy findings in AHT are not pathognomonic and, due to frequent obfuscation by perpetrators, the circumstances surrounding the alleged abuse are often unclear. The concept has evolved that the finding of the combination of subdural hemorrhage, brain injury, and retinal hemorrhages (“the triad”) is the result of shaking of an infant (“shaken baby syndrome”) and has led to the ongoing controversy whether shaking alone is able to generate sufficient force to produce these lesions. Objective In an attempt to investigate whether shaking can engender this lesion triad, animal models have been developed in laboratory rodents and domestic animal species. This review assesses the utility of these animal models to reliably reproduce human AHT pathology and evaluate the effects of shaking on the immature brain. Results Due largely to irreconcilable anatomic species differences between these animal brains and human infants, and a lack of resemblance of the experimental head shaking induced by mechanical devices to real-world human neurotrauma, no animal model has been able to reliably reproduce the full range of neuropathologic AHT changes. Conclusion Some animal models can simulate specific brain and ophthalmic lesions found in human AHT cases and provide useful information on their pathogenesis. Moreover, one animal model demonstrated that shaking of a freely mobile head, without an additional head impact, could be lethal, and produce significant brain pathology.
... 5 Such cases could be referred to as inflicted head injury by shaking trauma (IHI-ST). 6,7 Biomechanical experiments with manual shaking of surrogates/dummies equipped with sensors have been performed in previous studies, but the accelerations measured have been below the commonly applied injury thresholds for impact trauma in adults. [8][9][10][11] However, impact trauma differs largely from violent shaking events, especially concerning the duration of the acceleration peaks and the repeated loading due to the cyclic motion. ...
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Violent shaking is believed to be a common mechanism of injury in pediatric abusive head trauma. Typical intracranial injuries include subdural and retinal hemorrhages. Using a laboratory surrogate model we conducted experiments evaluating the head motion patterns that may occur in violent shaking. An anthropomorphic test device (ATD; Q0 dummy) matching an infant of 3.5?kg was assembled. The head interior was equipped with accelerometers enabling assessment of three-axial accelerations. Fifteen volunteers were asked to shake the surrogate vigorously holding a firm grip around the torso. We observed the volunteers performing manual shaking of the surrogate at a median duration of 15.5?sec (range 5?54?sec). Typical acceleration/deceleration patterns were produced after 2?3 shakes with a steady-state shaking motion at a pace of 4?6 cycles (back and forth) per second. Mean peak sagittal tangential accelerations at the vertex were 45.7g (range 14.2?105.1g). The acceleration component in the orthogonal direction, the radial acceleration, fluctuated around a negative mean of more than 4g showing that the surrogate head was continuously subjected to centripetal forces caused by rotations. This surrogate experiment showed that violent shaking may induce high peak tangential accelerations and concomitantly a continuous high-magnitude centripetal force. We hypothesize that the latter component may cause increased pressure in the subdural compartment in the cranial roof and may cause constant compression of the brain and possibly increased stretching or shearing of the bridging veins. This may contribute to the mechanism accountable for subdural hematoma in abusive head trauma.
... This can influence the level of force applied, how the energy is dissipated, and what the resulting injuries are. Ultimately, therefore, given the numerous difficulties involved in quantifying these variables, coupled with the uniqueness of the infant brain, it is not surprising that the injury patterns seen follow such a variable neuroimaging pattern [8,9]. ...
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The consequences of abusive head trauma (AHT) can be devastating for both the individual child and for wider society. Death is undoubtedly a very real possibility, but even for those children who survive, there is often very significant morbidity with the potential for gross motor and cognitive impairment, behavioural problems, blindness and epilepsy, which can greatly affect their quality of life. Caring for such children places a vast financial and infrastructural burden on society that frequently extends well into adulthood. While few struggle to have any sympathy for the perpetrator, frequently the infant’s father, it should be noted that a single solitary and momentary loss of complete control can have horrific and unforeseen consequences. A number of papers within this edition describe features of AHT and include descriptions of skull fractures and extra-axial haemorrhage, along with mimics of such phenomena. However, in this review we concentrate our attention on the myriad of parenchymal findings that can occur. Such parenchymal injuries include hypoxic–ischaemic damage, clefts, contusion and focal haemorrhage. We offer our perspectives on current thinking on these entities and put them in the context of the immensely important question — how do we recognise abusive head trauma?
... According to the recent literature there are two large peaks in pediatric TBI and the first one is in early childhood -0 to 4 years (74). The infant is highly susceptible to head trauma and brain injury is the most important outcome of head contusion (3,25,30,31,32,35,57). A study in 1995 has found that in a cohort of children suffering severe head injury prior to the age of 4 years none was able to work independently outside a structured environment years later, whereas children older than 4 years at the time of injury had a better outcome (48,74,75). ...
... Blunt impact injuries generally can be classified into four categories: contusion, abrasion, laceration, and fracture. 9,10,11 In this regard, currently, the classification of bruises is usually associated with the classification of injuries by hazard to human health, as recognized in forensic medicine and law enforcement agencies. 8 (Tabl. ...
... As described in part one of this review [1], inflicted head injury by shaking trauma in infants (IHI-ST) is a subject which has over the years given rise to much discussion in the scientific literature. While part one focuses on reviewing the literature on animal models for IHI-ST, in this paper a literature review is presented on mathematical and physical models that have been developed to understand IHI-ST. ...
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Various types of complex biomechanical models have been published in the literature to better understand processes related to inflicted head injury by shaking trauma (IHI-ST) in infants. In this systematic review, a comprehensive overview of these models is provided. A systematic review was performed in MEDLINE and Scopus for articles using physical (e.g. dolls) and mathematical (e.g. computer simulations) biomechanical models for IHI-ST. After deduplication, the studies were independently screened by two researchers using PRISMA methodology and data extracted from the papers is represented in a "7-steps description", addressing the different processes occurring during IHI-ST. Eleven papers on physical models and 23 papers on mathematical models were included after the selection process. In both categories, some models focus on describing gross head kinematics during IHI-ST events, while others address the behavior of internal head-and eye structures in various levels of detail. In virtually all physical and mathematical models analyzed, injury thresholds are derived from scaled non-infant data. Studies focusing on head kinematics often use injury thresholds derived from impact studies. It remains unclear to what extent these thresholds reflect the failure thresholds of infant biological material. Future research should therefore focus on investigating failure thresholds of infant biological material as well as on possible alternative injury mechanism and alternative injury criteria for IHI-ST.
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Biomedical Reviews is an official journal of the Bulgarian Society for Cell Biology published by the Medical University Press, Varna, Bulgaria. The Journal is published annually, and includes state-of-the-science (SOS) Reviews, Research Articles and Dance Round (a form of position papers) focused on disease-oriented molecular cell biology presented in concise form.....
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Repetitive back-and-forth head rotation due to vigorous shaking is purported to be a central mechanism responsible for diffuse white matter injury, subdural hemorrhage and retinal hemorrhage in some cases of abusive head trauma (AHT) in young children. Although animal studies have identified mechanisms of traumatic brain injury (TBI) associated with single rapid head acceleration-decelerations at levels experienced in a motor vehicle crash, few experimental studies have investigated TBI from repetitive head rotations. The objective of this study was to systematically investigate the post-injury pathological time-course after cyclic, low-velocity head rotations in the piglet, and compare them to single head rotations. Injury metrics were the occurrence and extent of axonal injury (AI), extra-axial hemorrhage (EAH), red cell neuronal/axonal change (RCNAC), and ocular injury (OI). Hyperflexion/extension of the neck were purposefully avoided in the study, resulting in unscaled angular accelerations at the lower end of reported infant surrogate shaking kinematics. All findings were at the mild end of the injury spectrum, with no significant findings at 6 hours post-injury. However, cyclic head rotations produced modest AI that significantly increased with time post-injury (p<0.035), and had significantly greater amounts of RCNAC and EAH than non-cyclic head rotations after 24 hours post-injury (p<0.05). No OI was observed. Future studies should investigate the contributions of additional physiological and mechanical features associated with AHT (e.g. hyperflexion/extension, increased intracranial pressure due to crying or thoracic compression, and more than two cyclic episodes) to enhance our understanding of the causality between proposed mechanistic factors and AHT in infants.
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For stroke and spinal cord injury, folic acid supplementation has been shown to enhance neurodevelopment and to provide neuroprotection. We hypothesized that folic acid would reduce brain injury and improve neurological outcome in a neonatal piglet model of traumatic brain injury (TBI), using 4 experimental groups of 3- to 5-day-old female piglets. Two groups were intubated, anesthetized and had moderate brain injury induced by rapid axial head rotation without impact. One group of injured (Inj) animals received folic acid (Fol; 80 μg/kg) by intraperitoneal (IP) injection 15 min following injury, and then daily for 6 days (Inj + Fol; n = 7). The second group of injured animals received an IP injection of saline (Sal) at the same time points (Inj + Sal; n = 8). Two uninjured (Uninj) control groups (Uninj + Fol, n = 8; Uninj + Sal, n = 7) were intubated, anesthetized and received folic acid (80 μg/kg) or saline by IP injection at the same time points as the injured animals following a sham procedure. Animals underwent neurobehavioral and cognitive testing on days 1 and 4 following injury to assess behavior, memory, learning and problem solving. Serum folic acid and homocysteine levels were collected prior to injury and again before euthanasia. The piglets were euthanized 6 days following injury, and their brains were perfusion fixed for histological analysis. Folic acid levels were significantly higher in both Fol groups on day 6. Homocysteine levels were not affected by treatment. On day 1 following injury, the Inj + Fol group showed significantly more exploratory interest, and better motor function, learning and problem solving compared to the Inj + Sal group. Inj + Fol animals had a significantly lower cognitive composite dysfunction score compared to all other groups on day 1. These functional improvements were not seen on day 4 following injury. Axonal injury measured by β-amyloid precursor protein staining 6 days after injury was not affected by treatment. These results suggest that folic acid may enhance early functional recovery in this piglet model of pediatric head injury. This is the first study to describe the application of complex functional testing to assess an intervention outcome in a swine model of TBI.
Object. Falls are the most common environmental setting for closed head injuries in children between 2 and 4 years of age. The authors previously found that toddlers had fewer skull fractures and scalp/facial soft-tissue injuries, and more frequent altered mental status than infants for the same low-height falls (≤ 3 ft). Methods. To identify potential age-dependent mechanical load factors that may be responsible for these clinical findings, the authors created an instrumented dummy representing an 18-month-old child using published toddler anthropometry and mechanical properties of the skull and neck, and they measured peak angular acceleration during low-height falls (1, 2, and 3 ft) onto carpet pad and concrete. They compared these results from occiput-first impacts to previously obtained values measured in a 6-week-old infant dummy. Results. Peak angular acceleration of the toddler dummy head was largest in the sagittal and horizontal directions and increased significantly (around 2-fold) with fall height between 1 and 2 ft. Impacts onto concrete produced larger peak angular accelerations and smaller impact durations than those onto carpet pad. When compared with previously measured infant drops, toddler head accelerations were more than double those of the infant from the same height onto the same surface, likely contributing to the higher incidence of loss of consciousness reported in toddlers. Furthermore, the toddler impact forces were larger than those in the infant, but because of the thicker toddler skull, the risk of skull fracture from low-height falls is likely lower in toddlers compared with infants. Conclusions. If similar fracture limits and brain tissue injury thresholds between infants and toddlers are assumed, it is expected that for impact events, the toddler is likely less vulnerable to skull fracture but more vulnerable to neurological impairment compared with the infant.
Expression of the immediate early gene, c-fos, was examined in a large animal model of non-accidental head injury ("shaken baby syndrome"). Lambs were used because they have a relatively large gyrencephalic brain and weak neck muscles resembling a human infant. Neonatal lambs were manually shaken in a manner similar to that believed to occur with most abused human infants, but there was no head impact. The most striking c-fos expression was in meningothelial cells of the cranial cervical spinal cord and, to a lesser degree, in hemispheric, cerebellar, and brainstem meninges. Vascular endothelial cells also frequently showed c-fos immunopositivity in the meninges and hemispheric white matter. It was hypothesised that this c-fos immunoreactivity was due to mechanical stress induced by shaking, with differential movement of different craniospinal components.
Objective: Abusive head trauma (AHT) is a leading cause of severe injury in maltreated children in the United States. There is little research from nationally representative datasets available to characterize young children who had AHT compared to non-abusive head trauma (NAHT). Methods: Using the recent CDC AHT case definition, we performed a retrospective analysis of 2000, 2003, 2006 and 2009 hospitalization data using the Kids' Inpatient Database (KID) from the Healthcare Cost and Utilization Project. Logistic regression was used to compare AHT to NAHT patients <2 years of age. Socio-demographic data and indicators of socioeconomic status (i.e., insurance status and household income), presence of chronic conditions, injury severity (i.e., length of hospital stay and vital status), hospital specialization (i.e., hospital type), hospital region, and season of admission were used as independent variables. Results: A weighted sample of 7,603 AHT and 25,339 NAHT patients was identified. National rates for AHT were 39.8 per 100,000 population for children <1 year and 6.8 per 100,000 population for children 1 year old. Compared to NAHT, children with AHT were more often <1 year of age (adjusted odds ratio [aOR]=2.66; 95% confidence interval [CI]: 2.35-3.01), male (aOR=1.10; 95% CI: 1.01-1.20), enrolled in Medicaid (aOR=2.78; 95% CI: 2.49-3.11), hospitalized longer (aOR=8.26; 95% CI: 7.24-9.43), died during hospitalization (aOR=5.12; 95% CI: 4.01-6.53), and seen at children's hospitals (aOR=1.97; 95% CI: 1.63-2.38) and hospitals outside the Northeast [aOR=2.65 (95% CI: 2.10-3.33) for the Midwest, 1.90 (95% CI: 1.52-2.38) for the South and 1.93 (95% CI: 1.45-2.57) for the West, respectively]. Conclusions: The results confirm that injuries from AHT are more severe and more often lethal than other head injuries. Socioeconomically disadvantaged families with children <1 year are an important focus for primary prevention. The associations of AHT, compared to NAHT with hospital type and hospital region warrant further investigation. Referral or reporting patterns, or true differences in the incidence may contribute to the identified associations.
Traumatic brain injury is a leading cause of death and disability in infants worldwide. Injury mechanisms include mechanical and biological insults, but few studies have examined the interaction between these mechanisms. We investigated the effect of head rotation direction on inertial brain injury in neonatal piglets using animal experiments and finite element (FE) modeling. We hypothesized that brain asymmetries lead to direction-dependent differences in tissue strains, cerebral blood flow (CBF), and histopathological responses to rotational injury. We developed and partially validated a FE model of the piglet brain and skull with an interface representative of meningeal tissues. We developed an efficient histological fluorescent microsphere technique using fluorescent imaging technology and automated analysis software to facilitate measurement of CBF changes. We observed direction-dependent differences in mechanical, physiological, and histopathological responses to a single sagittal, horizontal, or coronal head rotation. Sagittal rotations produced physiological derangements indicating medullary dysfunction and correspondingly high medullary strains. Sagittal rotations also produced significant regional CBF reductions compared to sham and the highest regional tissue strains. Coronal rotations produced no apparent physiological changes compared to sham and resulted in the lowest tissue strains. Horizontal rotations produced more variable physiological outcomes intermediate between those of sagittal and coronal, as well as intermediate tissue strains. For all injured animals, lower regional CBF correlated with higher tissue strains. Significant regional axonal injury resulted from sagittal and horizontal but not coronal rotations. Regional axonal injury frequently occurred in the absence of ischemia and correlated with regional tissue strains but not with regional CBF reductions. Tissue infarction was observed in sagittal and horizontal but not coronal animals, was always accompanied by axonal injury, and correlated with regional strains but not with 1 hour post-injury regional CBF reductions. The strain threshold for 50% probability of infarction was twice as high as that for axonal injury, consistent with these observations. We conclude that early axonal injury following trauma is due to mechanical rather than ischemic mechanisms. Recognizing the effect of head rotation direction on injury outcomes improves our understanding of brain injury mechanisms and leads to the development of better injury prevention and treatment strategies.